Docetaxel Zentiva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate contains 20 mg docetaxel (as trihydrate). 
 
One vial of 1 ml of concentrate contains 20 mg of docetaxel. 
 
Excipient with known effect: 
Each vial of concentrate contains 0.5 ml of ethanol anhydrous (395 mg).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is a pale yellow to brownish-yellow solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide is indicated for the 
adjuvant treatment of patients with: 

 operable node-positive breast cancer 
 operable node-negative breast cancer . 

 
For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 
patients eligible to receive chemotherapy according to internationally established criteria for primary 
therapy of early breast cancer (see section 5.1). 
 
Docetaxel Zentiva in combination with doxorubicin is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 
this condition. 
 
Docetaxel Zentiva monotherapy is indicated for the treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 
included an anthracycline or an alkylating agent. 
 
Docetaxel Zentiva in combination with trastuzumab is indicated for the treatment of patients with 
metastatic breast cancer whose tumours over express HER2 and who previously have not received 
chemotherapy for metastatic disease. 
 
Docetaxel Zentiva in combination with capecitabine is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 
should have included an anthracycline. 
 



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Non-small cell lung cancer 
 
Docetaxel Zentiva is indicated for the treatment of patients with locally advanced or metastatic 
non-small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Zentiva in combination with cisplatin is indicated for the treatment of patients with 
unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 
previously received chemotherapy for this condition. 
 
Prostate cancer 
 
Docetaxel Zentiva in combination with prednisone or prednisolone is indicated for the treatment of 
patients with metastatic castration-resistant prostate cancer. 
 
Docetaxel Zentiva in combination with androgen-deprivation therapy (ADT), with or without 
prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-
sensitive prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 
patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 
junction, who have not received prior chemotherapy for metastatic disease. 
 
Head and neck cancer 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the induction 
treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 
 
4.2 Posology and method of administration 
 
The use of docetaxel should be confined to units specialised in the administration of cytotoxic 
chemotherapy and it should only be administered under the supervision of a physician qualified in the 
use of anticancer chemotherapy (see section 6.6). 
 
Posology 
 
For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 
corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 
docetaxel administration, unless contraindicated, can be used (see section 4.4).  
For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 
prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 
and 1 hour before the docetaxel infusion (see section 4.4). 
For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 
prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 
and 1 hour before docetaxel infusion (see section 4.4). 
 
Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 
 
Docetaxel is administered as a one-hour infusion every three weeks. 
 
Breast cancer 
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 
dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 
500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment).  



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For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 
combination therapy with doxorubicin (50 mg/m2).  
 
In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 
with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 
the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 
immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 
well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 
characteristics. 
 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, 
see capecitabine summary of product characteristics. 
 
Non-small cell lung cancer 
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 
is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 
after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 
agent. 
 
Prostate cancer  
Metastatic castration-resistant prostate cancer 
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
Metastatic hormone-sensitive prostate cancer 
The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 
prednisolone 5 mg orally twice daily may be administered continuously. 
 
Gastric adenocarcinoma 
The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 
75 mg/m2, as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 
day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 
Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 
appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 
risk of haematological toxicities (see also Dose adjustments during treatment). 
 
Head and neck cancer 
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 
cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 
toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 
prophylactic antibiotics. 
 
 Induction chemotherapy followed by radiotherapy (TAX 323) 

For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 
and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 
followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 
continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 
3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.  

 
 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 

For the induction treatment of patients with locally advanced (technically unresectable, low 
probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 
head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour intravenous 
infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour 



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infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. 
This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should 
receive chemoradiotherapy. 

 
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 
characteristics. 
 
Dose adjustments during treatment 
 
General  
Docetaxel should be administered when the neutrophil count is  1,500 cells/mm3.  
In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 
one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 
therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 
60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 
discontinued.  
 
Adjuvant therapy for breast cancer 
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 
cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 
neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 
subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 
have their dose decreased to 60 mg/m². 
 
In combination with cisplatin 
For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 
nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 
experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 
dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 
corresponding summary of product characteristics. 
 
In combination with capecitabine 
 For capecitabine dose modifications, see capecitabine summary of product characteristics. 
 For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 

next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 
100% of the original dose.  

 For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1 
and then resume treatment with docetaxel 55 mg/m².  

 For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 
For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 
 
In combination with cisplatin and 5-fluorouracil 
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 
G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 
complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 
Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 
not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 
> 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these 
toxicities persist (see section 4.4). 
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 
cisplatin and 5-fluorouracil (5-FU): 
 

Toxicity Dose adjustment 
Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%.



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Second episode: then reduce docetaxel dose by 20%.
Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment.
Stomatitis/mucositis 
grade 3  

First episode: reduce 5-FU dose by 20%. 
Second episode: stop 5-FU only, at all subsequent cycles. 
Third episode: reduce docetaxel dose by 20%.

Stomatitis/mucositis 
grade 4 

First episode: stop 5-FU only, at all subsequent cycles. 
Second episode: reduce docetaxel dose by 20%.

 
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 
characteristics. 
 
In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 
neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 
prophylactic coverage (eg, day 6-15) in all subsequent cycles. 
 
Special populations 
 
Patients with hepatic impairment 
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 
elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 
range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 
docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 
ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-
reduction can be recommended and docetaxel should not be used unless strictly indicated.  
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Paediatric population 
The safety and efficacy of Docetaxel Zentiva in nasopharyngeal carcinoma in children aged 1 month 
to less than 18 years have not yet been established. 
There is no relevant use of Docetaxel Zentiva in the paediatric population in the indications breast 
cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 
including type II and III less differentiated nasopharyngeal carcinoma.  
 
Older people  
Based on a population pharmacokinetic analysis, there are no special instructions for use in the older 
people. 
In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 
capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 
 
Method of administration 
For instructions on preparation and administration of the product, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Patients with baseline neutrophil count of < 1,500 cells/mm3. 
 
Patients with severe liver impairment (see sections 4.2 and 4.4). 
 
Contraindications for other medicinal products also apply, when combined with docetaxel. 



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4.4 Special warnings and precautions for use 
 
For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 
dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 
administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 
as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 
dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2).  
 
Haematology 
 
Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 
of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 
complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 
retreated with docetaxel when neutrophils recover to a level  1,500 cells/mm3 (see section 4.2). 
 
In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 
docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 
symptomatic measures are recommended (see section 4.2). 
 
In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 
neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 
G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 
complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 
Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 
 
In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 
febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 
primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 
adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 
neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 
closely monitored (see sections 4.2 and 4.8). 
 
Gastrointestinal reactions 

 
Caution is recommended for patients with neutropenia, particularly at risk for developing 
gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 
docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 
as on the first day of onset. Patients should be closely monitored for early manifestations of serious 
gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 
 
Hypersensitivity reactions 
 
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 docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. Patients who have previously experienced a 
hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 
including more severe hypersensitivity reaction. These patients should be closely monitored during 
initiation of docetaxel therapy. 
 
Cutaneous reactions 
 



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Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 
followed by desquamation has been observed. Severe symptoms such as eruptions followed by 
desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 
section 4.2).  
 
Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 
reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 
serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 
appear, discontinuation of docetaxel should be considered. 
 
Fluid retention 
 
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 
monitored closely. 
 
Respiratory disorders 
 
Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 
pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 
outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 
investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 
diagnosis is available. Early use of supportive care measures may help improve the condition. The 
benefit of resuming docetaxel treatment must be carefully evaluated. 
 
Patients with liver impairment 
 
In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 
(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 
greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 
toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 
infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 
in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 
baseline and before each cycle (see section 4.2). 
For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 
with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 
and docetaxel should not be used unless strictly indicated. 
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Patients with renal impairment 
 
There are no data available in patients with severely impaired renal function treated with docetaxel.  
 
Nervous system 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 
 



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Cardiac toxicity 
 
Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 
particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 
be moderate to severe and has been associated with death (see section 4.8). 
 
When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 
should undergo baseline cardiac assessment. Cardiac function should be further monitored during 
treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 
more details see summary of product characteristics of trastuzumab. 
 
Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 
patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 
cyclophosphamide (see section 4.8).  
Baseline cardiac assessment is recommended. 
 
Eye disorders 
 
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 
4.8). 
 
Second primary malignancies 
 
Second primary malignancies have been reported when docetaxel was given in combination with 
anticancer treatments known to be associated with second primary malignancies.  Second primary 
malignancies (including acute myeloid leukaemia, myelodysplastic syndrome and non-Hodgkin 
lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 
monitored for second primary malignancies (see section 4.8). 
 
Others 
 
Contraceptive measures must be taken by both men and women during treatment and for men at least  
6 months after cessation of therapy (see section 4.6). 
 
The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 
clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 
voriconazole) should be avoided (see section 4.5). 
 
Additional cautions for use in adjuvant treatment of breast cancer 
 
Complicated neutropenia 
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 
 
Gastrointestinal reactions 
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 
 
Congestive heart failure (CHF) 
Patients should be monitored for symptoms of congestive heart failure during therapy and during the 
follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 
CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 
 
Patients with 4+ nodes 



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As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 
nodes was not fully demontrated at the final analysis (see section 5.1). 
 
 
 
 
 
 
Elderly 
 
 
Cautions for use in adjuvant treatment of breast cancer 
There are limited data available in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Cautions for use in castration-resistant prostate cancer 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study (TAX 327), 
209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients 
treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate 
 10% higher in patients who were 65 years of age or greater compared to younger patients. The 
incidence of related fever, diarrhoea, anorexia, and peripheral oedema occurred at rates  10% higher 
in patients who were 75 years of age or greater versus less than 65 years. 
 
Cautions for use in hormone-sensitive prostate cancer 
Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 
(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 
older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 
neutropenia, anemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 
less than 65 years. None of these increases in frequency reached 10% difference with control arm. In 
patients who were 75 years of age or older, when compared to younger patients, neutropenia, anemia, 
diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence (at least 
10% higher).  
 
Cautions for use in gastric adenocarcinoma cancer 
Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 
patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 
study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 
serious adverse events was higher in the older people compared to younger patients. The incidence of 
the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 
 10% higher in patients who were 65 years of age or older compared to younger patients.  
Older people treated with TCF should be closely monitored. 
 
Excipients 
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol 
anhydrous  per vial, equivalent to 10 ml of beer or 4 ml wine. 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as 
patients with liver disease, or epilepsy. 
 
Consideration should be given to possible effects on the central nervous system. 
 



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4.5 Interaction with other medicinal products and other forms of interaction 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 
a result, caution should be exercised when treating patients with these medicinal products as 
concomitant therapy since there is a potential for a significant interaction. 
 
In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 
increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 
ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 
telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 
dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 
(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 
the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 
49%. 
Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 
prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 
No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal product has not been investigated formally, in vitro interactions 
with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 
phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 
docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 
influence the binding of digitoxin. 
 
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 
co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 
between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 
about 50% higher than values previously reported for carboplatin monotherapy. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 
both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other 
cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated. 
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
Breast-feeding 
 
Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 
Consequently, because of the potential for adverse reactions in nursing infants, breast-feeding must be 
discontinued for the duration of docetaxel therapy. 
 
Contraception in males and females 
 
An effective method of contraception should be used during treatment. 
 



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Fertility 
 
In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 
Therefore, men being treated with docetaxel 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.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. The amount of 
alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 
use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 
of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 
machines, and be advised not to drive or use machines if they experience these side effects during 
treatment. 
 
4.8 Undesirable effects 
 
Summary of the safety profile for all indications 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in:  

 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

 258 patients who received docetaxel in combination with doxorubicin.  
 406 patients who received docetaxel in combination with cisplatin.  
 92 patients treated with docetaxel in combination with trastuzumab.  
 255 patients who received docetaxel in combination with capecitabine. 
 332 patients (TAX327) who received docetaxel in combination with prednisone or 

prednisolone (clinically important treatment related adverse events are presented). 
 1276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 

docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 
treatment related adverse events are presented). 

 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 
5-fluorouracil (clinically important treatment related adverse events are presented). 

 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are 
presented). 

 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 
grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are 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 available 
data). 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 
reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 
neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 
and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 
combination with other chemotherapeutic agents. 
 



13 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 
was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 
trastuzumab combination arm compared to docetaxel monotherapy. 
 
For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 
reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 
capecitabine summary of product characteristics). 
 
For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 
occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher incidence in the 
docetaxel treatment arm by comparison to the control arm, are presented, using the CTCAE grading 
scale. 
 
The following adverse reactions are frequently observed with docetaxel: 
 
Immune system disorders 
 
Hypersensitivity reactions have generally occurred within a few minutes following the start of the 
infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 
were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 
Severe reactions were characterised by hypotension and/or bronchospasm or generalized 
rash/erythema (see section 4.4). 
 
Nervous system disorders 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 
4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain 
including burning. Neuro-motor events are mainly characterised by weakness. 
 
Skin and subcutaneous tissue disorders 
 
Reversible cutaneous reactions have been observed and were generally considered as mild to 
moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 
hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 
associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 
Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 
interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 
nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis.  
 
General disorders and administration site conditions 
 
Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 
redness or dryness of the skin, phlebitis or extravasation and swelling of the vein. 
Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 
pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 
extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 
cumulative in incidence and severity (see section 4.4). 
 



14 

Tabulated summary of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m2 
single agent 
MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infections (G3/4: 5.7%; 
including sepsis and 
pneumonia, fatal in 
1.7%)  

Infection associated 
with G4 neutropenia 
(G3/4: 4.6%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
76.4%);  
Anaemia (G3/4: 8.9%); 
Febrile neutropenia

Thrombocytopenia (G4: 
0.2%) 

 

Immune system 
disorders 

Hypersensitivity (G3/4: 
5.3%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 4.1%); 
Peripheral motor 
neuropathy (G3/4: 4%); 
Dysgeusia (severe: 
0.07%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension;  
Hypertension; 
Haemorrhage

 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe: 
2.7%) 

  

Gastrointestinal 
disorders 

Stomatitis (G3/4: 
5.3%);  
Diarrhoea (G3/4: 4%);  
Nausea (G3/4: 4%);  
Vomiting (G3/4: 3%) 

Constipation (severe: 
0.2%);  
Abdominal pain 
(severe: 1%);  
Gastrointestinal 
haemorrhage (severe: 
0.3%)

Oesophagitis (severe: 
0.4%) 

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Skin reaction (G3/4: 
5.9%);  
Nail disorders (severe: 
2.6%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 1.4%) Arthralgia  

General disorders and 
administration site 
conditions 

Fluid retention (severe: 
6.5%); 
Asthenia (severe: 
11.2%);  
Pain 

Infusion site reaction;  
Non-cardiac chest pain 
(severe: 0.4%) 

 

Investigations  G3/4 Blood bilirubin 
increased (< 5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 4%); 

 



15 

MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

G3/4 AST increased 
(< 3%); 
G3/4 ALT increased 
(< 2%)

 
Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² single 
agent 
 
Blood and lymphatic system disorders 
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia. 
 
Nervous system disorders 
Reversibility data are available among 35.3% of patients who developed neurotoxicity following 
docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 
3 months. 
 
Skin and subcutaneous tissue disorders 
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 
were reversible within 21 days. 
 
General disorders and administration site conditions 
The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 
time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 
severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 
compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 
has been reported in some patients during the early courses of therapy. 
 



16 

Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² 
single agent 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Infections (G3/4: 5%)
Blood and lymphatic system 
disorders 

Neutropenia (G4: 54.2%);  
Anaemia (G3/4: 10.8%); 
Thrombocytopenia (G4: 1.7%)

Febrile neutropenia 

Immune system disorders  Hypersensitivity (no severe)
Metabolism and nutrition 
disorders 

Anorexia  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 0.8%)

Peripheral motor neuropathy 
(G3/4: 2.5%) 

Cardiac disorders  Arrhythmia (no severe)  
Vascular disorders  Hypotension 
Gastrointestinal disorders Nausea (G3/4: 3.3%);  

Stomatitis (G3/4: 1.7%);  
Vomiting (G3/4: 0.8%);  
Diarrhoea (G3/4: 1.7%)

Constipation 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Skin reaction (G3/4: 0.8%)

Nail disorders (severe: 0.8%) 

Musculoskeletal and connective 
tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

Asthenia (severe: 12.4%);  
Fluid retention (severe: 0.8%); 
Pain 

 

Investigations  G3/4 Blood bilirubin increased 
(< 2%)

 



17 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with doxorubicin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 7.8%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
91.7%); 
Anaemia (G3/4: 9.4%); 
Febrile neutropenia; 
Thrombocytopenia (G4: 
0.8%) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
1.2%)

 

Metabolism and 
nutrition disorders 

 Anorexia  

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Cardiac disorders  Cardiac failure;  
Arrhythmia (no severe)

 

Vascular disorders  Hypotension 
Gastrointestinal 
disorders 

Nausea (G3/4: 5%);  
Stomatitis (G3/4: 
7.8%);  
Diarrhoea (G3/4: 6.2%); 
Vomiting (G3/4: 5%);  
Constipation 

  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.4%);  
Skin reaction (no 
severe) 

  

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  

General disorders and 
administration site 
conditions 

Asthenia (severe: 
8.1%);  
Fluid retention (severe: 
1.2%); 
Pain 

Infusion site reaction  

Investigations  G3/4 Blood bilirubin 
increased (< 2.5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 2.5%)

G3/4 AST increased 
(< 1%); 
G3/4 ALT increased 
(< 1%) 

 



18 

Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 5.7%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
51.5%);  
Anaemia (G3/4: 6.9%); 
Thrombocytopenia (G4: 
0.5%) 

Febrile neutropenia  

Immune system 
disorders 

Hypersensitivity (G3/4: 
2.5%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 3.7%); 
Peripheral motor 
neuropathy (G3/4: 2%)

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension (G3/4: 
0.7%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 9.6%);  
Vomiting (G3/4: 7.6%); 
Diarrhoea (G3/4: 6.4%); 
Stomatitis (G3/4: 2%)

Constipation  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.7%);  
Skin reaction (G3/4: 
0.2%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 0.5%)   

General disorders and 
administration site 
conditions 

Asthenia (severe: 
9.9%); 
Fluid retention (severe: 
0.7%); 
Fever (G3/4: 1.2%)

Infusion site reaction;  
Pain 

 

Investigations  G3/4 Blood bilirubin 
increased (2.1%); 
G3/4 ALT increased 
(1.3%) 

G3/4 AST increased 
(0.5%);  
G3/4 Blood alkaline 
phosphatase increased 
(0.3%) 

 



19 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² in combination 
with trastuzumab 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Febrile neutropenia (includes 
neutropenia associated with 
fever and antibiotic use) or 
neutropenic sepsis 

 

Metabolism and nutrition 
disorders 

Anorexia  

Psychiatric disorders Insomnia
Nervous system disorders Paresthesia; Headache; 

Dysgeusia; Hypoaesthesia
 

Eye disorders Lacrimation increased; 
Conjunctivitis

 

Cardiac disorders  Cardiac failure 
Vascular disorders Lymphoedema
Respiratory, thoracic and 
mediastinal disorders 

Epistaxis; Pharyngolaryngeal 
pain; Nasopharyngitis; 
Dyspnoea;  
Cough; Rhinorrhoea

 

Gastrointestinal disorders Nausea; Diarrhoea; Vomiting; 
Constipation; Stomatitis; 
Dyspepsia; Abdominal pain

 

Skin and subcutaneous tissue 
disorders 

Alopecia; Erythema; Rash; Nail 
disorders

 

Musculoskeletal and connective 
tissue disorders 

Myalgia; Arthralgia; Pain in 
extremity; Bone pain; Back pain

 

General disorders and 
administration site conditions 

Asthenia; Oedema peripheral; 
Pyrexia; Fatigue; Mucosal 
inflammation; Pain; Influenza 
like illness; Chest pain; Chills

Lethargy 

Investigations Weight increased
 
Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² in 
combination with trastuzumab 
 
Blood and lymphatic system disorders 
Very common: Haematological toxicity was increased in patients receiving trastuzumab and 
docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 
criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 
known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 
incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 
Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 
 
Cardiac disorders 
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 
trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 
64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 
alone. 
 



20 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with capecitabine 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations  Oral candidiasis (G3/4: < 1%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 63%); 
Anaemia (G3/4: 10%)

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

Anorexia (G3/4: 1%);  
Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 
Paraesthesia (G3/4: < 1%) 

Dizziness;  
Headache (G3/4: < 1%);  
Neuropathy peripheral 

Eye disorders Lacrimation increased
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain (G3/4: 
2%) 

Dyspnoea (G3/4: 1%);  
Cough (G3/4: < 1%);  
Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%);  
Diarrhoea (G3/4: 14%);  
Nausea (G3/4: 6%);  
Vomiting (G3/4: 4%);  
Constipation (G3/4: 1%);  
Abdominal pain (G3/4: 2%);  
Dyspepsia

Abdominal pain upper;  
Dry mouth 

Skin and subcutaneous tissue 
disorders 

Hand-foot syndrome (G3/4: 
24%); 
Alopecia (G3/4: 6%);  
Nail disorders (G3/4: 2%) 

Dermatitis;  
Rash erythematous (G3/4: 
< 1%);  
Nail discolouration;  
Onycholysis (G3/4: 1%) 

Musculoskeletal and connective 
tissue disorders 

Myalgia (G3/4: 2%);  
Arthralgia (G3/4: 1%)

Pain in extremity (G3/4: < 1%); 
Back pain (G3/4: 1%) 

General disorders and 
administration site conditions 

Asthenia (G3/4: 3%);  
Pyrexia (G3/4: 1%);  
Fatigue/weakness (G3/4: 5%);  
Oedema peripheral (G3/4: 1%)

Lethargy; 
Pain 

Investigations  Weight decreased; 
G3/4 Blood bilirubin increased 
(9%)

 



21 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for Docetaxel 
Zentiva 75 mg/m² in combination with prednisone or prednisolone 
 
MedDRA system organ classes 
 

Very common adverse 
reactions 
 

Common adverse reactions 
 

Infections and infestations Infection (G3/4: 3.3%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Anaemia (G3/4: 4.9%) 

Thrombocytopenia (G3/4: 
0.6%); 
Febrile neutropenia 

Immune system disorders  Hypersensitivity (G3/4: 0.6%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 0.6%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 1.2%); 
Dysgeusia (G3/4: 0%)

Peripheral motor neuropathy 
(G3/4: 0%) 

Eye disorders  Lacrimation increased (G3/4: 
0.6%)

Cardiac disorders  Cardiac left ventricular function 
decrease (G3/4: 0.3%) 

Respiratory, thoracic and 
mediastinal disorders 

 Epistaxis (G3/4: 0%); 
Dyspnoea (G3/4: 0.6%);  
Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%);  
Diarrhoea (G3/4: 1.2%);  
Stomatitis/Pharyngitis (G3/4: 
0.9%);  
Vomiting (G3/4: 1.2%)

 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Nail disorders (no severe)

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

 Arthralgia (G3/4: 0.3%);  
Myalgia (G3/4: 0.3%) 

General disorders and 
administration site conditions 

Fatigue (G3/4: 3.9%); 
Fluid retention (severe: 0.6%)

 

 
Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 
prostate cancer for DOCETAXEL 75 mg/m² in combination with prednisone or prednisolone and 
ADT (STAMPEDE study)  
 
MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Blood and lymphatic system 
disorders 

Neutropenia (G3-4: 12 %) 
Anaemia  
Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 
disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  



22 

MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Nervous system disorders Peripheral sensory neuropathy 
(≥G3: 2%)a 
Headache 
 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

Respiratory, thoracic and 
mediastinal disorders  

Dyspnea (G3: 1%) 
Coughing (G3: 0%) 
Upper respiratory tract infection 
(G3: 1%) 

Pharyngitis (G3: 0%) 
 
 

Gastrointestinal disorders  Diarrhea (G3: 3%) 
Stomatitis (G3: 0%) 
Constipation (G3: 0%) 
Nausea (G3: 1%) 
Dyspepsia 
Abdominal pain (G3: 0%) 
Flatulence

Vomiting (G3: 1%) 
 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3: 3%)a 
Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 
connective tissue disorders 

Myalgia   

General disorders and 
administration site conditions 

Lethargy (G3-4: 2%) 
Flu-like symptoms (G3: 0%) 
Asthenia (G3: 0%) 
Fluid retention 

Fever (G3: 1%) 
Oral candidiasis  
Hypocalcaemia (G3: 0%) 
Hypophosphataemia (G3-4: 1%) 
Hypokalaemia (G3: 0%) 

 
 
a From the GETUG AFU15 study 
 



23 

Tabulated list of adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer - pooled data 
 
MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 2.4%); 
Neutropenic infection 
(G3/4: 2.6%) 
 

  

Blood and lymphatic 
system disorders 

Anaemia (G3/4: 3%);  
Neutropenia (G3/4: 
59.2%); 
Thrombocytopenia 
(G3/4: 1.6%);  
Febrile neutropenia 
(G3/4: NA) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
0.6%)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 1.5%)   

Nervous system 
disorders 

Dysgeusia (G3/4: 
0.6%); 
Peripheral sensory 
neuropathy (G3/4: 
<0.1%) 

Peripheral motor 
neuropathy (G3/4: 0%)  

Syncope (G3/4: 0%); 
Neurotoxicity (G3/4: 
0%);  
Somnolence (G3/4: 0%)

Eye disorders Conjunctivitis (G3/4: 
<0.1%) 

Lacrimation increased 
(G3/4: <0.1%)  

 

Cardiac disorders  Arrhythmia (G3/4: 
0.2%)  

 

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension (G3/4: 
0%); 
Phlebitis (G3/4: 0%)

Lymphoedema (G3/4: 
0%) 

Respiratory, thoracic 
and mediastinal 
disorders 

 Cough (G3/4: 0%)  

Gastrointestinal 
disorders 

Nausea (G3/4: 5.0%); 
Stomatitis (G3/4: 
6.0%);  
Vomiting (G3/4: 4.2%); 
Diarrhoea (G3/4: 3.4%);
Constipation (G3/4: 
0.5%)  

Abdominal pain (G3/4: 
0.4%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (persisting: 
<3%);  
Skin disorder (G3/4: 
0.6%);  
Nail disorders (G3/4: 
0.4%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (G3/4: 0.7%); 
Arthralgia (G3/4: 0.2%)

  



24 

MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Reproductive system 
and breast disorders 

Amenorrhoea (G3/4: 
NA) 

  

General disorders and 
administration site 
conditions 

Asthenia (G3/4: 
10.0%); 
Pyrexia (G3/4: NA); 
Oedema peripheral 
(G3/4: 0.2%) 

  

Investigations  Weight increased (G3/4: 
0%); 
Weight decreased 
(G3/4: 0.2%)

 

 
Description of selected adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer  
 
Nervous system disorders 
In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 
the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 
of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 
observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 
In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 
persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 
arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 
sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 
(0.2%) in FAC arm. 
 
Cardiac disorders 
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 
congestive heart failure during the follow-up period. At the end of the follow-up period (actual median 
follow-up time of 10 years and 5 months), no patients  had CHF in TAC arm and 1 patient in TAC arm 
died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient (0.2%) in 
FAC arm. 
 
Skin and subcutaneous tissue disorders 
In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 
At the end of the follow-up period (actual median follow-up time of	8 years), alopecia was observed to 
be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-
up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 
FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 
42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 
period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 
patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm. 
Reproductive system and breast disorders 
In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 
FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 
(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 



25 

In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 
follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 
in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 
amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 
FAC arm. 
 
General disorders and administration site conditions 
In study TAX316 peripheral oedema that started during the treatment period and persisted into the 
follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 
23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 
years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  
In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-
up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 
FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 
lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 
In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 
FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 
asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
 
In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 
follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 
the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 
had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 
Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 
(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 
lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 
FAC arm.  
Asthenia that started during the treatment period and persisted into the follow-up period was observed 
to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 
follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 
patients (0.4%) in FAC arm. 
 
Acute leukaemia / Myelodysplastic syndrome. 
After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 
(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 
syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 
After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 
patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 
myelodysplastic syndrome in either treatment groups. 
 
Neutropenic complications 
Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 
infection was decreased in patients who received primary G-CSF prophylaxis after it was made 
mandatory in the TAC arm – GEICAM study. 
 



26 

Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 
(GEICAM 9805) 
 
 Without primary 

G-CSF prophylaxis 
(n = 111) 

n (%) 

With primary  
G-CSF prophylaxis 

(n = 421)  
n (%) 

Neutropenia (Grade 4)  104 (93.7) 135 (32.1) 
 

Febrile neutropenia  28 (25.2) 23 (5.5) 
 

Neutropenic infection  14 (12.6) 21 (5.0) 
 

Neutropenic infection 
(Grade 3-4)  

2 (1.8) 5 (1.2) 

 
Tabulated list of adverse reactions in gastric adenocarcinoma cancer for Docetaxel Zentiva 75 mg/m² 
in combination with cisplatin and 5-fluorouracil 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Neutropenic infection; 
Infection (G3/4: 11.7%)

 

Blood and lymphatic system 
disorders 

Anaemia (G3/4: 20.9%); 
Neutropenia (G3/4: 83.2%);  
Thrombocytopenia (G3/4: 
8.8%); 
Febrile neutropenia 

 

Immune system disorders Hypersensitivity (G3/4: 1.7%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 11.7%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%);  
Peripheral motor neuropathy 
(G3/4: 1.3%) 

Eye disorders  Lacrimation increased (G3/4: 
0%)

Ear and labyrinth disorders  Hearing impaired (G3/4: 0%)
Cardiac disorders  Arrhythmia (G3/4: 1.0%) 
Gastrointestinal disorders Diarrhoea (G3/4: 19.7%);  

Nausea (G3/4: 16%);  
Stomatitis (G3/4: 23.7%); 
Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 
Gastrointestinal pain (G3/4: 
1.0%); 
Oesophagitis/dysphagia/odynop
hagia (G3/4: 0.7%) 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%);  
Nail disorders (G3/4: 0.7%);  
Skin exfoliation (G3/4: 0%)

General disorders and 
administration site conditions 

Lethargy (G3/4: 19.0%); 
Fever (G3/4: 2.3%); 
Fluid retention (severe/life-
threatening: 1%)

 

 



27 

Description of selected adverse reactions in gastric adenocarcinoma cancer for Docetaxel Zentiva 
75 mg/m² in combination with cisplatin and 5-fluorouracil 
 
Blood and lymphatic system disorders 
Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 
regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 
the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 
patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 
prophylactic G-CSF (see section 4.2). 
 
Tabulated list of adverse reactions in head and neck cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin and 5-fluorouracil 
 
 Induction chemotherapy followed by radiotherapy (TAX 323) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 6.3%); 
Neutropenic infection

  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
0.6%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
76.3%); 
Anaemia (G3/4: 9.2%); 
Thrombocytopenia 
(G3/4: 5.2%) 

Febrile neutropenia  

Immune system 
disorders 

 Hypersensitivity (no 
severe)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 0.6%)   

Nervous system 
disorders 

Dysgeusia/Parosmia; 
Peripheral sensory 
neuropathy (G3/4: 
0.6%) 

Dizziness  

Eye disorders  Lacrimation increased; 
Conjunctivitis 

 

Ear and labyrinth 
disorders 

 Hearing impaired  

Cardiac disorders  Myocardial ischemia 
(G3/4:1.7%)

Arrhythmia (G3/4: 
0.6%) 

Vascular disorders  Venous disorder (G3/4: 
0.6%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 0.6%); 
Stomatitis (G3/4: 
4.0%); 
Diarrhoea (G3/4: 2.9%);
Vomiting (G3/4: 0.6%) 

Constipation; 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
0.6%); 
Abdominal pain; 
Dyspepsia; 
Gastrointestinal 
haemorrhage (G3/4: 
0.6%) 

 



28 

MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 
Dry skin;  
Skin exfoliative (G3/4: 
0.6%)

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.6%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 3.4%); 
Pyrexia (G3/4: 0.6%); 
Fluid retention; 
Oedema 

  

Investigations  Weight increased
 
 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 3.6%) 
 

Neutropenic infection  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
1.2%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
83.5%); 
Anaemia (G3/4: 
12.4%); 
Thrombocytopenia 
(G3/4: 4.0%); 
Febrile neutropenia

  

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 
12.0%) 

  

Nervous system 
disorders 

Dysgeusia/Parosmia 
(G3/4: 0.4%); 
Peripheral sensory 
neuropathy (G3/4: 
1.2%) 

Dizziness (G3/4: 
2.0%); 
Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
2.0%)

Ischemia myocardial 

Vascular disorders  Venous disorder



29 

MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Gastrointestinal 
disorders 

Nausea (G3/4: 13.9%); 
Stomatitis (G3/4: 
20.7%); 
Vomiting (G3/4: 
8.4%); 
Diarrhoea (G3/4: 
6.8%); 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
12.0%); 
Constipation (G3/4: 
0.4%) 

Dyspepsia (G3/4: 
0.8%); 
Gastrointestinal pain 
(G3/4: 1.2%); 
Gastrointestinal 
haemorrhage (G3/4: 
0.4%) 
 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 4.0%); 
Rash pruritic 

Dry skin ; 
Desquamation

 

Musculoskeletal, 
connective tissue bone 
disorders 

 Myalgia (G3/4: 0.4%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 4.0%); 
Pyrexia (G3/4: 3.6%); 
Fluid retention (G3/4: 
1.2%); 
Oedema (G3/4: 1.2%)

  

Investigations Weight decreased Weight increased
 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 
Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 
reported in association with docetaxel when used in combination with other anticancer treatments 
known to be associated with second primary malignancies. Acute myeloid leukaemia and 
myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 
breast cancer with TAC regimen. 
 
Blood and lymphatic system disorders 
Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been 
reported. 
 
Immune system disorders 
Some cases of anaphylactic shock, sometimes fatal, have been reported. 
Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 
previously experienced hypersensitivity reactions to paclitaxel. 
 
Nervous system disorders 
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 
administration. These reactions sometimes appear during the infusion of the medicinal product. 
 
Eye disorders 
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 
during infusion of the medicinal product and in association with hypersensitivity reactions have been 
reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 
without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 
rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 
docetaxel. 



30 

 
Ear and labyrinth disorders 
Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 
 
Cardiac disorders 
Rare cases of myocardial infarction have been reported. 
Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 
been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-
fluorouracil and/ or cyclophosphamide. 
 
Vascular disorders 
Venous thromboembolic events have rarely been reported. 
 
Respiratory, thoracic and mediastinal disorders 
Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.  
 
Gastrointestinal disorders 
Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 
reported with a potential fatal outcome (frequency not known). 
Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 
including enterocolitis and gastrointestinal perforation.  
Rare cases of ileus and intestinal obstruction have been reported. 
 
Hepatobiliary disorders 
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 
 
Skin and subcutaneous tissue disorders  
Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 
cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 
(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel. 
Sclerodermal-like changes usually preceded by peripheral lymphoedema have been reported with 
docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 
 
Renal and urinary disorders 
Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 
risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and gastro-
intestinal disorders. 
 
General disorders and administration site conditions 
Radiation recall phenomena have rarely been reported. 
Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 
administration of docetaxel at a different site) has been observed at the site of previous extravasation 
(frequency not known). 
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 
 
Metabolism and nutrition disorders 
Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 
mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 
hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 
with diarrhoea. 
 
Reporting of suspected adverse reactions 



31 

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 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Taxanes, ATC Code: L01CD02 
 
Mechanism of action 
 
Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 
microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 
binding of docetaxel to microtubules does not alter the number of protofilaments. 
 
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 
vital mitotic and interphase cellular functions.  
 
Pharmacodynamic effects 
 
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 
against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 
concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 
but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 
gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour 
activity against advanced murine and human grafted tumours. 
 
Clinical efficacy and safety 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide: adjuvant therapy 
 
Patients with operable node-positive breast cancer (TAX 316) 
 
Data from a multi-centre open label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS  80%, between 18 and 
70 years of age. After stratification according to the number of positive lymph nodes (1-3, 4+), 
1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 
doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 
followed by fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 (FAC arm). Both regimens 
were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 
all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 
secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 
prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 



32 

ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 
both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 
receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 
according to guidelines in place at participating institutions and was given to 69% of patients who 
received TAC and 72% of patients who received FAC.  
Two interim analyses and one final analysis were performed. The first interim analysis was planned 
3 years after the date when half of study enrolment was done. The second interim analysis was done 
after 400 DFS events had been recorded overall, which led to a median follow-up of 55 months. The 
final analysis was performed when all patients had reached their 10-year follow-up visit (unless they 
had a DFS event or were lost to follow-up before). Disease-free survival (DFS) was the primary 
efficacy endpoint and overall survival (OS) was the secondary efficacy endpoint. 
 
A final analysis was performed with an actual median follow-up of 96 months. Significantly longer 
disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 
relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 
(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 
10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 
i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 
with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 
patients with 4+ nodes was not fully demonstrated at the final analysis. 
 
Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analysed: 
 
  Disease free survival Overall survival 
Patient subset Number 

of 
patients 

Hazard 
ratio* 

95% CI p = Hazard 
ratio* 

95% CI p = 

No of positive 
nodes 

       

Overall 745 0.80 0.68-0.93 0.0043 0.74 0.61-0.90 0.0020
1-3 467 0.72 0.58-0.91 0.0047 0.62 0.46-0.82 0.0008
4+ 278 0.87 0.70-1.09 0.2290 0.87 0.67-1.12 0.2746
*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 
overall survival compared to FAC 
 
Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805)  
 
Data from a multi-centre open label randomised trial support the use of Docetaxel Zentiva for the 
adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 
chemotherapy . 1060 patients were randomised to receive either Docetaxel Zentiva 75 mg/m2 
administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 
TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclophosphamide 
500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 
patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size >2 cm and/or 
negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age <35 years).). 
Both regimens were administered once every 3 weeks for 6 cycles. Docetaxel Zentiva was 
administered as a 1-hour infusion, all other medicinal products were given intravenously on day 1 
every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 
were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 
was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 
after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 
20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 
guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 
and 51.2% of patients who received FAC. 



33 

 
One primary analysis and one updated analysis were performed. The primary analysis was done when 
all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 
analysis was performed when all patients had reached their 10-year (median follow up time of 10 
years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 
previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 
was the secondary efficacy endpoint. 
 
At the median follow-up time of 77 months, significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). At the 
median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% reduction in the 
risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 
p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 
favour of TAC.   
  
At the median follow-up time of 77 months, overall survival (OS) was longer in the TAC arm with 
TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard 
ratio = 0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly 
different between the 2 groups. 
At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 
the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  
The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 
point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 
 
The positive benefit risk ratio for TAC compared to FAC remained unchanged.   
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 
in the primary analysis (at the median follow-up time of 77 months) (see table below): 



34 

 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study  
(Intent-to-Treat Analysis) 

 
  Disease Free Survival 
Patient subset Number of patients 

in TAC group 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1   
<50 years 260 0.67 0.43-1.05 
≥50 years 279 0.67 0.43-1.05 
Age category 2   
<35 years 42 0.31 0.11-0.89 
≥35 years 497 0.73 0.52-1.01 
Hormonal receptor 
status 

   

Negative 195 0.7 0.45-1.1 
Positive 344 0.62 0.4-0.97 
Tumour size    
2 cm 285 0.69 0.43-1.1 
>2 cm 254 0.68 0.45-1.04 
Histological grade   
Grade1 (includes grade 
not assessed) 

64 0.79 0.24-2.6 

Grade 2 216 0.77 0.46-1.3 
Grade 3 259 0.59 0.39-0.9 
Menopausal status   
Pre-Menopausal 285 0.64 0.40-1 
Post-Menopausal 254 0.72 0.47-1.12 
*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free survival 
compared to FAC. 
 
Exploratory subgroup analyses for disease-free survival for patients who meet the 2009 St. Gallen 
chemotherapy criteria – (ITT population) were performed and presented here below: 
 
  

TAC 
 

FAC 
Hazard ratio 
(TAC/FAC) 

 
 

Subgroups (n=539) (n=521) (95% CI) p-value
 
Meeting relative indication 
for chemotherapy a 

    

 
No 

 
18/214 
(8.4%)

 
26/227 
(11.5%)

 
0.796 (0.434 - 1.459) 

 
0.4593 

 
Yes 

 
48/325 
(14.8%)

 
69/294 
(23.5%)

 
0.606 (0.42 - 0.877) 

 
0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 
FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 
CI = confidence interval; ER = oestrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 



35 

Docetaxel Zentiva as single agent 
 
Two randomised phase III comparative studies, involving a total of 326 alkylating or 
392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 
recommended dose and regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 
time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 
response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 
p = 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 
15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 
failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 
(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p = 0.0004) and 
prolonged overall survival (11 months vs. 9 months, p = 0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 
observed in phase II studies (see section 4.8).  
 
An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 
therapy should have included an anthracycline. A total of 449 patients were randomised to receive 
either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 
infusion. Both regimens were administered every 3 weeks. 
Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 
prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 
(15.3 months vs 12.7 months; p = 0.03). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%).  
 
Docetaxel Zentiva in combination with doxorubicin 
 
One large randomised phase III study, involving 429 previously untreated patients with metastatic 
disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 
(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) 
(AC arm). Both regimens were administered on day 1 every 3 weeks. 
 
 Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 
27.4 - 36.0) in AC arm. 
 Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC arm. 
 
In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 
neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 
(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 
higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 
incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 
decrease  20% (13.1% versus 6.1%), absolute LVEF decrease  30% (6.2% versus 1.1%). Toxic 
deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 
(1 due to septic shock and 3 due to congestive heart failure). 
In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 
treatment and follow-up. 
 



36 

Docetaxel Zentiva in combination with trastuzumab 
 
Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 
breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 
for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 
(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 
chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 
received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 
this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 
fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 
and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 
summarized in the following table: 
 

Parameter Docetaxel plus trastuzumab1 
n = 92

Docetaxel1 
n = 94 

Response rate  
(95% CI) 

61% 
(50-71)

34% 
(25-45) 

Median duration of response 
(months) 
(95% CI) 

 
11.4 

(9.2-15.0)

 
5.1 

(4.4-6.2) 
Median TTP (months) 
(95% CI) 

10.6 
(7.6-12.9)

5.7 
(5.0-6.5) 

Median survival (months) 
(95% CI) 

30.52 
(26.8-ne)

22.12 
(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached. 
1Full analysis set (intent-to-treat) 
2 Estimated median survival 

 
Docetaxel Zentiva in combination with capecitabine 
 
Data from one multi-centre, randomised, controlled phase III clinical study support the use of 
docetaxel in combination with capecitabine for treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 
study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 
infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 
rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 
intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 
combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 
(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 
assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 
progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 
median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 
 
Non-small cell lung cancer 
 
Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 
and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 
Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 
There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 
disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 
docetaxel at 75 mg/m² compared to those with BSC. 
The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 
26.1 weeks. 
 



37 

Docetaxel Zentiva in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 
administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 
day 1 of cycles repeated every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated 
in the following table: 
 

 TCis 
n = 408

VCis 
n = 404

Statistical analysis 

Overall survival  
(Primary end-point):

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 
[97.2% CI: 0.937; 1.342]*

1-year Survival (%) 46 41 Treatment difference: 5.4% 
[95% CI: -1.1; 12.0] 

2-year Survival (%) 21 14 Treatment difference: 6.2% 
[95% CI: 0.2; 12.3] 

Median time to progression 
(weeks): 

 
22.0 

 
23.0 

 
Hazard Ratio: 1.032 

[95% CI: 0.876; 1.216] 
Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 
*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 
region of treatment), based on evaluable patient population. 

 
Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnofsky performance status. Results on these end-points 
were supportive of the primary end-points results.  
 
For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 
compared to the reference treatment combination VCis. 
 
Prostate cancer 
 
Metastatic castration-resistant prostate cancer 
 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 
study (TAX 327). A total of 1006 patients with KPS  60 were randomised to the following treatment 
groups: 
 Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 
 Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 
 Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 
continuously. 
 
Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 
compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 
arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 
the docetaxel arms versus the control arm are summarized in the following table: 



38 

 
Endpoint 
 

Docetaxel  
every 3 weeks 

Docetaxel  
every week

Mitoxantrone  
every 3 weeks

Number of patients 
Median survival (months) 
95% CI 
Hazard ratio 
95% CI 
p-value†* 

335 
18.9 

(17.0-21.2) 
0.761 

(0.619-0.936) 
0.0094

334 
17.4 

(15.7-19.0) 
0.912 

(0.747-1.113) 
0.3624

337 
16.5 

(14.4-18.6) 
-- 
-- 
-- 

Number of patients 
PSA** response rate (%) 
95% CI 
p-value* 

291 
45.4 

(39.5-51.3) 
0.0005

282 
47.9 

(41.9-53.9) 
<0.0001

300 
31.7 

(26.4-37.3) 
-- 

Number of patients 
Pain response rate (%) 
95% CI 
p-value* 

153 
34.6 

(27.1-42.7) 
0.0107

154 
31.2 

(24.0-39.1) 
0.0798

157 
21.7 

(15.5-28.9) 
-- 

Number of patients 
Tumour response rate (%) 
95% CI 
p-value* 

141 
12.1 

(7.2-18.6) 
0.1112 

134 
8.2 

(4.2-14.2) 
0.5853 

137 
6.6 

(3.0-12.1) 
-- 

†Stratified log rank test 
*Threshold for statistical significance = 0.0175 
**PSA: Prostate-Specific Antigen 
 
Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 
3 weeks, it is possible that certain patients may benefit from docetaxel every week. 
 
No statistical differences were observed between treatment groups for Global Quality of Life. 
 
Metastatic hormone-sensitive prostate cancer 
STAMPEDE study 
 
The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 
patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 
evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 
II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  
 Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles    
 Standard of care alone  
Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 
continuously.  
Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 
docetaxel in combination with standard of care, 724 received standard of care alone.  
In these metastatic prostate cancer patients, the median overall survival was significantly longer in 
docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 
months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 
p=0.005).  
 
Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 
summarized in the following table: 
 
 



39 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 
treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 
 

Endpoint 
 

Docetaxel + standard of care 
 

Standard of care alone 

Number of metastatic prostate 
cancer patients 
Median overall survival (months)  
95% CI 

362 
 

62 
51-73

724 
 

43 
40-48 

Adjusted hazard ratio 
95% CI 
p-valuea 

0.76 
(0.62-0.92) 

0.005 

Failure-Free survivalb    
Median (months) 
95% CI 
 

20.4 
16.8-25.2 

12 
9.6-12 

 
Adjusted hazard ratio 
95% CI 
p-valuea 

0.66 
(0.57-0.76) 

< 0.001 
a p-value calculated from the likelihood ratio test and adjusted for all stratification 
factors (except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 
failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 
and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 
metastases; skeletal-related event; or death from prostate cancer. 
 

 
 
CHAARTED study 
 
The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 
(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 
Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 
treatment groups.  

 ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 
for 6 cycles 

 ADT alone   
 
The median overall survival was significantly longer in docetaxel treatment group than in the ADT 
alone group, with a median overall survival 13.6 months  longer with the addition of docetaxel to ADT 
(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  
 
Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 
 



40 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 
cancer (CHAARTED) 
 

Endpoint 
 

Docetaxel +ADT  
 

ADT alone 

Number of patients 
Median overall survival (months) 
All patients 
95% CI 
Adjusted hazard ratio 

397 
 

57.6 
49.1-72.8 

0.61 

393 
 

44.0 
34.4-49.1 

-- 
95% CI (0.47-0.80)  --
p-valuea 0.0003 -- 
Progression Free Survival 
Median (months) 
95% CI 
Adjusted hazard ratio 
95% CI 
p-value* 

 
19.8 

16.7-22.8 
0.60 

0.51-0.72 
P<0.0001 

 
11.6 

10.8-14.3 
-- 
-- 
-- 

PSA response** at 6 months – N(%) 
p-valuea* 

127 (32.0) 
<0.0001 

77 (19.6) 
-- 

PSA response** at 12 months – N(%) 
p-valuea* 

110 (27.7) 
<0.0001 

66 (16.8) 
-- 

Time to castration-resistant prostate cancerb   
Median (months)  
95% CI 
Adjusted hazard ratio 

20.2 
(17.2-23.6) 

0.61 

11.7 
(10.8-14.7) 

-- 
95% CI (0.51-0.72) --
p-valuea* <0.0001 -- 

Time to clinical progressionc    
Median (months)  33.0 19.8
95% CI (27.3-41.2) (17.9-22.8)
Adjusted hazard ratio 0.61 -- 
95% CI (0.50-0.75) --
p-valuea* <0.0001 -- 
a Time to event variables: Stratified log-rank test.  
  Response rate variables: Fisher's Exact test  
* p-value for descriptive purpose. 
** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 
consecutive measurements at least 4 weeks apart. 
b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 
clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 
Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer per the 
Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 
increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 
due to cancer according to the investigator’s opinion).
 
 
Gastric adenocarcinoma 
 
A multi-centre, open-label, randomised study was conducted to evaluate the safety and efficacy of 
docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 
adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 



41 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 
(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 
(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 
day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 
arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 
arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 
endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 
TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 
(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 
summarized in the following table: 
 
Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 
Endpoint TCF 

n = 221
CF 

n = 224 
Median TTP (months) 5.6 3.7 
(95% CI) (4.86-5.91) (3.45-4.47) 
Hazard ratio 1.473 
(95% CI) (1.189-1.825) 
*p-value 0.0004 
Median survival (months) 9.2 8.6 
(95% CI) (8.38-10.58) (7.16-9.46)
2-year estimate (%) 18.4 8.8 
Hazard ratio 1.293 
(95% CI) (1.041-1.606) 
*p-value 0.0201 
Overall response rate (CR+PR) (%) 36.7 25.4 
p-value 0.0106 
Progressive disease as best overall response (%) 16.7 25.9 

*Unstratified log rank test 
 
Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 
arm. 
 
A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 
a statistically significant difference although always in favour of the TCF regimen and showed that the 
benefit of TCF over CF is clearly observed between 18 and 30 months of follow up. 
 
Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 
of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 
health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 
Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 
 
Head and neck cancer 
 
 Induction chemotherapy followed by radiotherapy (TAX323) 
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 
carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 
randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO perfomance status 0 or 1, were randomised to one of two treatment arms. Patients on the 
docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 
5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 
administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 
bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 
a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 
progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 
Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 



42 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 
at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 
after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 
of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 
institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 
with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 
70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 
interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 
regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 
chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 
with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 
The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 
TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 
overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 
favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 
28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below: 
 
Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 
(Intent-to-Treat Analysis) 
 
Endpoint Docetaxel + 

Cis + 5-FU 
n = 177 

Cis + 5-FU 
 

n = 181 
Median progression free survival (months) 
(95% CI) 

11.4 
(10.1-14.0)

8.3 
(7.4-9.1) 

Adjusted hazard ratio 
(95% CI) 
*p-value 

0.70 
(0.55-0.89) 

0.0042 
Median survival (months) 
(95% CI) 

18.6 
(15.7-24.0)

14.5 
(11.6-18.7)

Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95% CI) 

67.8 
(60.4-74.6)

53.6 
(46.0-61.0)

***p-value 0.006 
Best overall response to study treatment 
[chemotherapy +/- radiotherapy] (%) 
(95% CI) 

 
72.3 

(65.1-78.8)

 
58.6 

(51.0-65.8)
***p-value 0.006 
Median duration of response to chemotherapy  
radiotherapy (months) 
(95% CI) 

n = 128 
15.7 

(13.4-24.6) 

n = 106 
11.7 

(10.2-17.4) 
Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.52-0.99) 

0.0457 
A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 
**Log rank test 
*** Chi-square test 

 
Quality of life parameters 
 
Patients treated with TPF experienced significantly less deterioration of their Global health score 
compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale).  
 
Clinical benefit parameters 



43 

 
The performance status scale, for head and neck (PSS-HN) subscales designed to measure 
understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 
of TPF as compared to PF. 
Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 
compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 
pain management. 
 
 Induction chemotherapy followed by chemoradiotherapy (TAX324) 
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 
squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 
open-label, phase III study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 
a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 
comprised patients with technically unresectable disease, patients with low probability of surgical cure 
and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 
endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 
arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 
100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 
intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 
repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 
chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 
cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 
continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 
were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 
receive CRT as per protocol (PF/CRT).  
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 
with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 
day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 
intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 
using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 
70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at any time 
following completion of CRT. All patients on the docetaxel-containing arm of the study received 
prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 
significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 
(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 
to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 
follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 
progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 
PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 
p = 0.004. Efficacy results are presented in the table below: 
 



44 

Efficacy of docetaxel in the induction treatment of patients  
with locally advanced SCCHN (Intent-to-Treat Analysis) 
 

Endpoint Docetaxel + Cis + 5-FU 
n = 255 

Cis + 5-FU 
n = 246 

Median overall survival (months)  
(95% CI) 

70.6 
(49.0-NA)

30.1 
(20.9-51.5) 

Hazard ratio: 
(95% CI) 
*p-value  

0.70 
(0.54-0.90) 

0.0058
Median PFS (months)  
(95% CI) 

35.5 
(19.3-NA)

13.1 
(10.6 - 20.2) 

Hazard ratio: 
(95% CI) 
**p-value  

0.71 
(0.56 - 0.90) 

0.004
Best overall response (CR + PR) to 
chemotherapy (%) 
(95% CI) 

71.8 
(65.8-77.2) 

64.2 
(57.9-70.2) 

***p-value 0.070
Best overall response (CR + PR) to study 
treatment [chemotherapy +/- 
chemoradiotherapy] (%) 
(95%CI) 

76.5 
(70.8-81.5) 

71.5 
(65.5-77.1) 

***p-value 0.209
A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil 
*un-adjusted log-rank test 
**un-adjusted log-rank test, not adjusted for multiple comparisons 
***Chi square test, not adjusted for multiple comparisons 
NA-not applicable 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Docetaxel Zentiva in all subsets of the paediatric population in breast cancer, non-small cell lung 
cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less 
differentiated nasopharyngeal carcinoma (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 
20-115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent 
with a three-compartment pharmacokinetic model with half-lives for the ,  and  phases of 4 min, 
36 min and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel 
from the peripheral compartment.  
 
Distribution 
 
Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 
level of 3.7 µg/ml was obtained with a corresponding AUC of 4.6 h.µg/ml. Mean values for total body 
clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 
individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 
bound to plasma proteins. 
 



45 

Elimination 
 
A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 
both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 
ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 
the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 
excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 
and very low amounts of unchanged medicinal product. 
Special populations  
 
Age and gender 
A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 
Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 
studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient.  
 
Hepatic impairment 
In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 
function impairment (ALT, AST  1.5 times the ULN associated with alkaline phosphatase 
 2.5 times the ULN), total clearance was lowered by 27% on average (see section 4.2).  
 
Fluid retention 
Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 
no data available in patients with severe fluid retention. 
 
Combination therapy 
 
Doxorubicin 
When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 
levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 
and cyclophosphamide were not influenced by their co-administration. 
 
Capecitabine 
Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 
showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 
effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5’-DFUR. 
 
Cisplatin 
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 
similar to that observed with cisplatin alone. 
 
Cisplatin and 5-fluorouracil 
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 
tumours had no influence on the pharmacokinetics of each individual medicinal product. 
 
Prednisone and dexamethasone 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 
dexamethasone premedication has been studied in 42 patients.  
 
Prednisone 
No effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
5.3 Preclinical safety data 
 
The carcinogenic potential of docetaxel has not been studied. 
 



46 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 
test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 
mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 
with the pharmacological activity of docetaxel. 
 
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair 
male fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polysorbate 80 
Ethanol anhydrous 
Citric acid 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf-life 
 
Unopened vial 
2 years 
 
After opening of the vial 
Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user.  
 
Once added to the infusion bag  
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions and the medicinal product should be used immediately. If not used immediately, in-use 
storage times and conditions are the responsibility of the user. 
 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 
25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 
intravenous administration).  
 
In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 
has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded.  
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Store in the original package in order to protect from light. 
 
For storage conditions of the diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
7 ml clear glass (type I) vial with a green aluminium seal and a green plastic flip-off cap containing 
1 ml of concentrate. 



47 

 
Each box contains one vial. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Zentiva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Zentiva solutions. The use of gloves is 
recommended. 
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If Docetaxel Zentiva concentrate or infusion 
solution should come into contact with mucous membranes, wash immediately and thoroughly with 
water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion, 
which contains only 1 vial). 
 
Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution. 
 
Each vial is of single use and should be used immediately. 
 
If the vials are stored under refrigeration, allow the required number of boxes of Docetaxel Zentiva 
concentrate for solution for infusion to stand below 25°C for 5 minutes before use. 
More than one vial of Docetaxel Zentiva concentrate for solution for infusion may be necessary to 
obtain the required dose for the patient. Aseptically withdraw the required amount of Docetaxel 
Zentiva concentrate for solution for infusion using a calibrated syringe fitted with a 21G needle. 
 
In Docetaxel Zentiva 20 mg /1 ml vial the concentration of docetaxel is 20 mg/ml. 
The required volume of Docetaxel Zentiva concentrate for solution for infusion must be injected via a 
single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose solution 
or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 
that a concentration of 0.74 mg/ml docetaxel is not exceeded.  
 
Mix the infusion bag or bottle manually using a rocking motion. 
 
The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 
to the patient. 
As with all parenteral products, Docetaxel Zentiva infusion solution should be visually inspected prior 
to use, solutions containing a precipitate should be discarded. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Zentiva k.s., U kabelovny 130, 102 37 Prague 10, Czech Republic 
 



48 

8. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 April 2007 
Date of latest renewal: 20 April 2012 
 
 
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.  
 



49 

1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate contains 20 mg docetaxel (as trihydrate). 
 
One vial of 4 ml of concentrate contains 80 mg of docetaxel. 
 
Excipient with known effect: 
Each vial of concentrate contains 2 ml of ethanol anhydrous (1.58 g).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is a pale yellow to brownish-yellow solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide is indicated for the 
adjuvant treatment of patients with: 

 operable node- positive breast cancer 
 operable node-negative breast cancer . 

 
For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 
patients eligible to receive chemotherapy according to internationally established criteria for primary 
therapy of early breast cancer (see section 5.1). 
Docetaxel Zentiva in combination with doxorubicin is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 
this condition. 
 
Docetaxel Zentiva monotherapy is indicated for the treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 
included an anthracycline or an alkylating agent. 
 
Docetaxel Zentiva in combination with trastuzumab is indicated for the treatment of patients with 
metastatic breast cancer whose tumours over express HER2 and who previously have not received 
chemotherapy for metastatic disease. 
 
Docetaxel Zentiva in combination with capecitabine is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 
should have included an anthracycline. 
 



50 

Non-small cell lung cancer 
 
Docetaxel Zentiva is indicated for the treatment of patients with locally advanced or metastatic 
non-small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Zentiva in combination with cisplatin is indicated for the treatment of patients with 
unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 
previously received chemotherapy for this condition. 
 
Prostate cancer 
 
Docetaxel Zentiva in combination with prednisone or prednisolone is indicated for the treatment of 
patients with metastatic castration-resistant prostate cancer. 
 
Docetaxel Zentiva in combination with androgen-deprivation therapy (ADT), with or without 
prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-
sensitive prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 
patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 
junction, who have not received prior chemotherapy for metastatic disease. 
 
Head and neck cancer 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the induction 
treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 
 
4.2 Posology and method of administration 
 
The use of docetaxel should be confined to units specialised in the administration of cytotoxic 
chemotherapy and it should only be administered under the supervision of a physician qualified in the 
use of anticancer chemotherapy (see section 6.6). 
 
Posology 
 
For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 
corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 
docetaxel administration, unless contraindicated, can be used (see section 4.4).  
For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 
prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 
and 1 hour before the docetaxel infusion (see section 4.4). 
For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 
prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 
and 1 hour before docetaxel infusion (see section 4.4). 
 
Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 
 
Docetaxel is administered as a one-hour infusion every three weeks. 
 
Breast cancer 
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 
dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 
500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment).  



51 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 
combination therapy with doxorubicin (50 mg/m2).  
 
In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 
with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 
the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 
immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 
well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 
characteristics. 
 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, 
see capecitabine summary of product characteristics. 
 
Non-small cell lung cancer 
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 
is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 
after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 
agent. 
 
Prostate cancer  
Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
Metastatic hormone-sensitive prostate cancer 
The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 
prednisolone 5 mg orally twice daily may be administered continuously. 
 
Gastric adenocarcinoma 
The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 
75 mg/m2, as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 
day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 
Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 
appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 
risk of haematological toxicities (see also Dose adjustments during treatment). 
 
Head and neck cancer 
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 
cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 
toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 
prophylactic antibiotics. 
 
 Induction chemotherapy followed by radiotherapy (TAX 323) 

For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 
and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 
followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 
continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 
3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.  

 
 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 

For the induction treatment of patients with locally advanced (technically unresectable, low 
probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 
head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour intravenous 
infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour 



52 

infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. 
This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should 
receive chemoradiotherapy. 

 
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 
characteristics. 
 
Dose adjustments during treatment 
 
General  
Docetaxel should be administered when the neutrophil count is  1,500 cells/mm3.  
In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 
one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 
therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 
60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 
discontinued.  
 
Adjuvant therapy for breast cancer 
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 
cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 
neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 
subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 
have their dose decreased to 60 mg/m². 
 
In combination with cisplatin 
For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 
nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 
experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 
dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 
corresponding summary of product characteristics. 
 
In combination with capecitabine 
 For capecitabine dose modifications, see capecitabine summary of product characteristics. 
 For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 

next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 
100% of the original dose.  

 For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1 
and then resume treatment with docetaxel 55 mg/m².  

 For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 
For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 
 
In combination with cisplatin and 5-fluorouracil 
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 
G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 
complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 
Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 
not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 
> 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these 
toxicities persist (see section 4.4). 
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 
cisplatin and 5-fluorouracil (5-FU): 
 

Toxicity Dose adjustment 
Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%.



53 

Second episode: then reduce docetaxel dose by 20%.
Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment.
Stomatitis/mucositis 
grade 3  

First episode: reduce 5-FU dose by 20%. 
Second episode: stop 5-FU only, at all subsequent cycles. 
Third episode: reduce docetaxel dose by 20%.

Stomatitis/mucositis 
grade 4 

First episode: stop 5-FU only, at all subsequent cycles. 
Second episode: reduce docetaxel dose by 20%.

 
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 
characteristics. 
 
In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 
neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 
prophylactic coverage (eg, day 6-15) in all subsequent cycles. 
 
Special populations 
 
Patients with hepatic impairment 
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 
elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 
range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 
docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 
ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-
reduction can be recommended and docetaxel should not be used unless strictly indicated.  
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Paediatric population 
The safety and efficacy of Docetaxel Zentiva in nasopharyngeal carcinoma in children aged 1 month 
to less than 18 years have not yet been established. 
There is no relevant use of Docetaxel Zentiva in the paediatric population in the indications breast 
cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 
including type II and III less differentiated nasopharyngeal carcinoma.  
 
Older people  
Based on a population pharmacokinetic analysis, there are no special instructions for use in the older 
people. 
In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 
capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 
 
Method of administration 
For instructions on preparation and administration of the product, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Patients with baseline neutrophil count of < 1,500 cells/mm3. 
 
Patients with severe liver impairment (see sections 4.2 and 4.4). 
 
Contraindications for other medicinal products also apply, when combined with docetaxel. 



54 

 
4.4 Special warnings and precautions for use 
 
For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 
dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 
administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 
as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 
dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2).  
 
Haematology 
 
Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 
of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 
complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 
retreated with docetaxel when neutrophils recover to a level  1,500 cells/mm3 (see section 4.2). 
 
In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 
docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 
symptomatic measures are recommended (see section 4.2). 
 
In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 
neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 
G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 
complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 
Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 
 
In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 
febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 
primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 
adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 
neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 
closely monitored (see sections 4.2 and 4.8). 
 
Gastrointestinal reactions 

 
Caution is recommended for patients with neutropenia, particularly at risk for developing 
gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 
docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 
as on the first day of onset. Patients should be closely monitored for early manifestations of serious 
gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 
 
Hypersensitivity reactions 
 
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 docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. Patients who have previously experienced a 
hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 
including more severe hypersensitivity reaction. These patients should be closely monitored during 
initiation of docetaxel therapy. 
 
Cutaneous reactions 
 



55 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 
followed by desquamation has been observed. Severe symptoms such as eruptions followed by 
desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 
section 4.2).  
 
Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 
reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 
serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 
appear, discontinuation of docetaxel should be considered. 
 
Fluid retention 
 
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 
monitored closely. 
 
Respiratory disorders 
 
Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 
pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 
outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 
investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 
diagnosis is available. Early use of supportive care measures may help improve the condition. The 
benefit of resuming docetaxel treatment must be carefully evaluated. 
 
Patients with liver impairment 
 
In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 
(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 
greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 
toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 
infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 
in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 
baseline and before each cycle (see section 4.2). 
For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 
with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 
and docetaxel should not be used unless strictly indicated. 
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Patients with renal impairment 
 
There are no data available in patients with severely impaired renal function treated with docetaxel.  
 
Nervous system 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 
 



56 

Cardiac toxicity 
 
Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 
particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 
be moderate to severe and has been associated with death (see section 4.8). 
 
When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 
should undergo baseline cardiac assessment. Cardiac function should be further monitored during 
treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 
more details see summary of product characteristics of trastuzumab. 
 
Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 
patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 
cyclophosphamide (see section 4.8).  
Baseline cardiac assessment is recommended 
 
Eye disorders 
 
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 
4.8). 
 
Second primary malignancies 
 
Second primary malignancies have been reported when docetaxel was given in combination with 
anticancer treatments known to be associated with second primary malignancies.  Second primary 
malignancies (including acute myeloid leukaemia, myelodysplastic syndrome and non-Hodgkin 
lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 
monitored for second primary malignancies (see section 4.8). 
 
Others 
 
Contraceptive measures must be taken by both men and women during treatment and for men at least  
6 months after cessation of therapy (see section 4.6). 
 
The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 
clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 
voriconazole) should be avoided (see section 4.5). 
 
Additional cautions for use in adjuvant treatment of breast cancer 
 
Complicated neutropenia 
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 
 
Gastrointestinal reactions 
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 
 
Congestive heart failure (CHF) 
Patients should be monitored for symptoms of congestive heart failure during therapy and during the 
follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 
CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 
 
Patients with 4+ nodes 



57 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 
nodes was not fully demontrated at the final analysis (see section 5.1). 
 
 
 
 
 
Elderly 
 
Cautions for use in adjuvant treatment of breast cancer 
There are limited data available in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Cautions for use in castration-resistant prostate cancer 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study (TAX 327), 
209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients 
treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate 
 10% higher in patients who were 65 years of age or greater compared to younger patients. The 
incidence of related fever, diarrhoea, anorexia, and peripheral oedema occurred at rates  10% higher 
in patients who were 75 years of age or greater versus less than 65 years. 
 
Cautions for use in hormone-sensitive prostate cancer 
Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 
(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 
older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 
neutropenia, anemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 
less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 
In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 
anemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 
(at least 10% higher).  
 
Cautions for use in gastric adenocarcinoma cancer 
Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 
patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 
study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 
serious adverse events was higher in the older people compared to younger patients. The incidence of 
the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates 
 10% higher in patients who were 65 years of age or older compared to younger patients.  
Older people treated with TCF should be closely monitored. 
 
Excipients 
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1.58 g ethanol 
anhydrous  per vial, equivalent to 40 ml of beer or 17 ml wine. 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as 
patients with liver disease, or epilepsy. 
 
Consideration should be given to possible effects on the central nervous system. 
 



58 

4.5 Interaction with other medicinal products and other forms of interaction 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 
a result, caution should be exercised when treating patients with these medicinal products as 
concomitant therapy since there is a potential for a significant interaction. 
 
In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 
increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 
ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 
telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 
dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 
(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 
the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 
49%. 
Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 
prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 
No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal product has not been investigated formally, in vitro interactions 
with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 
phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 
docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 
influence the binding of digitoxin. 
 
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 
co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 
between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 
about 50% higher than values previously reported for carboplatin monotherapy. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 
both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other 
cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated. 
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
Breast-feeding 
 
Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 
Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 
discontinued for the duration of docetaxel therapy. 
 
Contraception in males and females 
 
An effective method of contraception should be used during treatment. 
 



59 

Fertility 
 
In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 
Therefore, men being treated with docetaxel 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.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. The amount of 
alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 
use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 
of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 
machines, and be advised not to drive or use machines if they experience these side effects during 
treatment. 
 
4.8 Undesirable effects 
 
Summary of the safety profile for all indications 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in:  

 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

 258 patients who received docetaxel in combination with doxorubicin.  
 406 patients who received docetaxel in combination with cisplatin.  
 92 patients treated with docetaxel in combination with trastuzumab.  
 255 patients who received docetaxel in combination with capecitabine. 
 332 patients (TAX327) who received docetaxel in combination with prednisone or 

prednisolone (clinically important treatment related adverse events are presented). 
 1276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 

docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 
treatment related adverse events are presented). 

 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 
5-fluorouracil (clinically important treatment related adverse events are presented). 

 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are 
presented). 

 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 
grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are 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 available 
data). 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 
reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 
neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 
and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 
combination with other chemotherapeutic agents. 
 



60 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 
was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 
trastuzumab combination arm compared to docetaxel monotherapy. 
 
For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 
reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 
capecitabine summary of product characteristics). 
 
For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 
occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher incidence in the 
docetaxel treatment arm by comparison to the control arm, are presented, using the CTCAE grading 
scale. 
 
The following adverse reactions are frequently observed with docetaxel: 
 
Immune system disorders 
 
Hypersensitivity reactions have generally occurred within a few minutes following the start of the 
infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 
were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 
Severe reactions were characterised by hypotension and/or bronchospasm or generalized 
rash/erythema (see section 4.4). 
 
Nervous system disorders 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 
4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain 
including burning. Neuro-motor events are mainly characterised by weakness. 
 
Skin and subcutaneous tissue disorders 
 
Reversible cutaneous reactions have been observed and were generally considered as mild to 
moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 
hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 
associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 
Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 
interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 
nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis.  
 
General disorders and administration site conditions 
 
Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 
redness or dryness of the skin, phlebitis or extravasation and swelling of the vein. 
Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 
pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 
extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 
cumulative in incidence and severity (see section 4.4). 
 
Tabulated summary of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² single 
agent 
 
MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infections (G3/4: 5.7%; 
including sepsis and 
pneumonia, fatal in 

Infection associated 
with G4 neutropenia 
(G3/4: 4.6%)

 



61 

MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

1.7%)  
Blood and lymphatic 
system disorders 

Neutropenia (G4: 
76.4%);  
Anaemia (G3/4: 8.9%); 
Febrile neutropenia

Thrombocytopenia (G4: 
0.2%) 

 

Immune system 
disorders 

Hypersensitivity (G3/4: 
5.3%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 4.1%); 
Peripheral motor 
neuropathy (G3/4: 4%); 
Dysgeusia (severe: 
0.07%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension;  
Hypertension; 
Haemorrhage

 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe: 
2.7%) 

  

Gastrointestinal 
disorders 

Stomatitis (G3/4: 
5.3%);  
Diarrhoea (G3/4: 4%);  
Nausea (G3/4: 4%);  
Vomiting (G3/4: 3%) 

Constipation (severe: 
0.2%);  
Abdominal pain 
(severe: 1%);  
Gastrointestinal 
haemorrhage (severe: 
0.3%)

Oesophagitis (severe: 
0.4%) 

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Skin reaction (G3/4: 
5.9%);  
Nail disorders (severe: 
2.6%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 1.4%) Arthralgia  

General disorders and 
administration site 
conditions 

Fluid retention (severe: 
6.5%); 
Asthenia (severe: 
11.2%);  
Pain 

Infusion site reaction;  
Non-cardiac chest pain 
(severe: 0.4%) 

 

Investigations  G3/4 Blood bilirubin 
increased (< 5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 4%);  
G3/4 AST increased 
(< 3%); 
G3/4 ALT increased 
(< 2%)

 

 



62 

Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m2 single 
agent 
 
Blood and lymphatic system disorders 
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia. 
 
Nervous system disorders 
Reversibility data are available among 35.3% of patients who developed neurotoxicity following 
docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 
3 months. 
 
Skin and subcutaneous tissue disorders 
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 
were reversible within 21 days. 
 
General disorders and administration site conditions 
The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 
time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 
severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 
compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 
has been reported in some patients during the early courses of therapy. 
 
Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² 
single agent 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Infections (G3/4: 5%)
Blood and lymphatic system 
disorders 

Neutropenia (G4: 54.2%);  
Anaemia (G3/4: 10.8%); 
Thrombocytopenia (G4: 1.7%)

Febrile neutropenia 

Immune system disorders  Hypersensitivity (no severe)
Metabolism and nutrition 
disorders 

Anorexia  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 0.8%)

Peripheral motor neuropathy 
(G3/4: 2.5%) 

Cardiac disorders  Arrhythmia (no severe)  
Vascular disorders  Hypotension 
Gastrointestinal disorders Nausea (G3/4: 3.3%);  

Stomatitis (G3/4: 1.7%);  
Vomiting (G3/4: 0.8%);  
Diarrhoea (G3/4: 1.7%)

Constipation 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Skin reaction (G3/4: 0.8%)

Nail disorders (severe: 0.8%) 

Musculoskeletal and connective 
tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

Asthenia (severe: 12.4%);  
Fluid retention (severe: 0.8%); 
Pain 

 

Investigations  G3/4 Blood bilirubin increased 
(< 2%)

 



63 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with doxorubicin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 7.8%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
91.7%); 
Anaemia (G3/4: 9.4%); 
Febrile neutropenia; 
Thrombocytopenia (G4: 
0.8%) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
1.2%)

 

Metabolism and 
nutrition disorders 

 Anorexia  

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Cardiac disorders  Cardiac failure;  
Arrhythmia (no severe)

 

Vascular disorders  Hypotension 
Gastrointestinal 
disorders 

Nausea (G3/4: 5%);  
Stomatitis (G3/4: 
7.8%);  
Diarrhoea (G3/4: 6.2%); 
Vomiting (G3/4: 5%);  
Constipation 

  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.4%);  
Skin reaction (no 
severe) 

  

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  

General disorders and 
administration site 
conditions 

Asthenia (severe: 
8.1%);  
Fluid retention (severe: 
1.2%); 
Pain 

Infusion site reaction  

Investigations  G3/4 Blood bilirubin 
increased (< 2.5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 2.5%)

G3/4 AST increased 
(< 1%); 
G3/4 ALT increased 
(< 1%) 

 



64 

Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 5.7%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
51.5%);  
Anaemia (G3/4: 6.9%); 
Thrombocytopenia (G4: 
0.5%) 

Febrile neutropenia  

Immune system 
disorders 

Hypersensitivity (G3/4: 
2.5%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 3.7%); 
Peripheral motor 
neuropathy (G3/4: 2%)

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension (G3/4: 
0.7%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 9.6%);  
Vomiting (G3/4: 7.6%); 
Diarrhoea (G3/4: 6.4%); 
Stomatitis (G3/4: 2%)

Constipation  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.7%);  
Skin reaction (G3/4: 
0.2%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 0.5%)   

General disorders and 
administration site 
conditions 

Asthenia (severe: 
9.9%); 
Fluid retention (severe: 
0.7%); 
Fever (G3/4: 1.2%)

Infusion site reaction;  
Pain 

 

Investigations  G3/4 Blood bilirubin 
increased (2.1%); 
G3/4 ALT increased 
(1.3%) 

G3/4 AST increased 
(0.5%);  
G3/4 Blood alkaline 
phosphatase increased 
(0.3%) 

 



65 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² in combination 
with trastuzumab 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Febrile neutropenia (includes 
neutropenia associated with 
fever and antibiotic use) or 
neutropenic sepsis 

 

Metabolism and nutrition 
disorders 

Anorexia  

Psychiatric disorders Insomnia
Nervous system disorders Paresthesia; Headache; 

Dysgeusia; Hypoaesthesia
 

Eye disorders Lacrimation increased; 
Conjunctivitis

 

Cardiac disorders  Cardiac failure 
Vascular disorders Lymphoedema
Respiratory, thoracic and 
mediastinal disorders 

Epistaxis; Pharyngolaryngeal 
pain; Nasopharyngitis; 
Dyspnoea;  
Cough; Rhinorrhoea

 

Gastrointestinal disorders Nausea; Diarrhoea; Vomiting; 
Constipation; Stomatitis; 
Dyspepsia; Abdominal pain

 

Skin and subcutaneous tissue 
disorders 

Alopecia; Erythema; Rash; Nail 
disorders

 

Musculoskeletal and connective 
tissue disorders 

Myalgia; Arthralgia; Pain in 
extremity; Bone pain; Back pain

 

General disorders and 
administration site conditions 

Asthenia; Oedema peripheral; 
Pyrexia; Fatigue; Mucosal 
inflammation; Pain; Influenza 
like illness; Chest pain; Chills

Lethargy 

Investigations Weight increased
 
Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m2 in 
combination with trastuzumab 
 
Blood and lymphatic system disorders 
Very common: Haematological toxicity was increased in patients receiving trastuzumab and 
docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 
criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 
known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 
incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 
Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 
 
Cardiac disorders 
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 
trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 
64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 
alone. 
 



66 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with capecitabine 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations  Oral candidiasis (G3/4: < 1%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 63%); 
Anaemia (G3/4: 10%)

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

Anorexia (G3/4: 1%);  
Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 
Paraesthesia (G3/4: < 1%) 

Dizziness;  
Headache (G3/4: < 1%);  
Neuropathy peripheral 

Eye disorders Lacrimation increased
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain (G3/4: 
2%) 

Dyspnoea (G3/4: 1%);  
Cough (G3/4: < 1%);  
Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%);  
Diarrhoea (G3/4: 14%);  
Nausea (G3/4: 6%);  
Vomiting (G3/4: 4%);  
Constipation (G3/4: 1%);  
Abdominal pain (G3/4: 2%);  
Dyspepsia

Abdominal pain upper;  
Dry mouth 

Skin and subcutaneous tissue 
disorders 

Hand-foot syndrome (G3/4: 
24%); 
Alopecia (G3/4: 6%);  
Nail disorders (G3/4: 2%) 

Dermatitis;  
Rash erythematous (G3/4: 
< 1%);  
Nail discolouration;  
Onycholysis (G3/4: 1%) 

Musculoskeletal and connective 
tissue disorders 

Myalgia (G3/4: 2%);  
Arthralgia (G3/4: 1%)

Pain in extremity (G3/4: < 1%); 
Back pain (G3/4: 1%) 

General disorders and 
administration site conditions 

Asthenia (G3/4: 3%);  
Pyrexia (G3/4: 1%);  
Fatigue/weakness (G3/4: 5%);  
Oedema peripheral (G3/4: 1%)

Lethargy; 
Pain 

Investigations  Weight decreased; 
G3/4 Blood bilirubin increased 
(9%)

 



67 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for Docetaxel 
Zentiva 75 mg/m² in combination with prednisone or prednisolone 
 
MedDRA system organ classes 
 

Very common adverse 
reactions 
 

Common adverse reactions 
 

Infections and infestations Infection (G3/4: 3.3%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Anaemia (G3/4: 4.9%) 

Thrombocytopenia (G3/4: 
0.6%); 
Febrile neutropenia 

Immune system disorders  Hypersensitivity (G3/4: 0.6%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 0.6%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 1.2%); 
Dysgeusia (G3/4: 0%)

Peripheral motor neuropathy 
(G3/4: 0%) 

Eye disorders  Lacrimation increased (G3/4: 
0.6%)

Cardiac disorders  Cardiac left ventricular function 
decrease (G3/4: 0.3%) 

Respiratory, thoracic and 
mediastinal disorders 

 Epistaxis (G3/4: 0%); 
Dyspnoea (G3/4: 0.6%);  
Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%);  
Diarrhoea (G3/4: 1.2%);  
Stomatitis/Pharyngitis (G3/4: 
0.9%);  
Vomiting (G3/4: 1.2%)

 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Nail disorders (no severe)

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

 Arthralgia (G3/4: 0.3%);  
Myalgia (G3/4: 0.3%) 

General disorders and 
administration site conditions 

Fatigue (G3/4: 3.9%); 
Fluid retention (severe: 0.6%)

 

 
Tabulated list of adverse reactions in high-risk locally advanced or metastatic hormone-sensitive 
prostate cancer for DOCETAXEL 75 mg/m² in combination with prednisone or prednisolone and 
ADT (STAMPEDE study)  
 
MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Blood and lymphatic system 
disorders 

Neutropenia (G3-4: 12 %) 
Anaemia  
Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 
disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  



68 

MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Nervous system disorders Peripheral sensory neuropathy 
(≥G3: 2%)a 
Headache 
 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

Respiratory, thoracic and 
mediastinal disorders  

Dyspnea (G3: 1%) 
Coughing (G3: 0%) 
Upper respiratory tract infection 
(G3: 1%) 

Pharyngitis (G3: 0%) 
 
 

Gastrointestinal disorders  Diarrhea (G3: 3%) 
Stomatitis (G3: 0%) 
Constipation (G3: 0%) 
Nausea (G3: 1%) 
Dyspepsia 
Abdominal pain (G3: 0%) 
Flatulence

Vomiting (G3: 1%) 
 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3: 3%)a 
Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 
connective tissue disorders 

Myalgia   

General disorders and 
administration site conditions 

Lethargy (G3-4: 2%) 
Flu-like symptoms (G3: 0%) 
Asthenia (G3: 0%) 
Fluid retention 

Fever (G3: 1%) 
Oral candidiasis  
Hypocalcaemia (G3: 0%) 
Hypophosphataemia (G3-4: 1%) 
Hypokalaemia (G3: 0%) 

 
 
a From the GETUG AFU15 study 



69 

Tabulated list of adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer - pooled data 
 
MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 

Uncommon adverse 
reactions 

Infections and 
infestations 

Infection (G3/4: 2.4%); 
Neutropenic infection 
(G3/4: 2.6%) 
 

  

Blood and lymphatic 
system disorders 

Anaemia (G3/4: 3%);  
Neutropenia (G3/4: 
59.2%); 
Thrombocytopenia 
(G3/4: 1.6%);  
Febrile neutropenia 
(G3/4: NA) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
0.6%)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 1.5%)   

Nervous system 
disorders 

Dysgeusia (G3/4: 
0.6%); 
Peripheral sensory 
neuropathy (G3/4: 
<0.1%) 

Peripheral motor 
neuropathy (G3/4: 0%)  

Syncope (G3/4: 0%); 
Neurotoxicity (G3/4: 
0%);  
Somnolence (G3/4: 0%)

Eye disorders Conjunctivitis (G3/4: 
<0.1%) 

Lacrimation increased 
(G3/4: <0.1%)  

 

Cardiac disorders  Arrhythmia (G3/4: 
0.2%)  

 

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension (G3/4: 
0%); 
Phlebitis (G3/4: 0%)

Lymphoedema (G3/4: 
0%) 

Respiratory, thoracic 
and mediastinal 
disorders 

 Cough (G3/4: 0%)  

Gastrointestinal 
disorders 

Nausea (G3/4: 5.0%); 
Stomatitis (G3/4: 
6.0%);  
Vomiting (G3/4: 4.2%); 
Diarrhoea (G3/4: 3.4%);
Constipation (G3/4: 
0.5%)  

Abdominal pain (G3/4: 
0.4%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (persisting: 
<3%);  
Skin disorder (G3/4: 
0.6%);  
Nail disorders (G3/4: 
0.4%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (G3/4: 0.7%); 
Arthralgia (G3/4: 0.2%)

  



70 

MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 

Uncommon adverse 
reactions 

Reproductive system 
and breast disorders 

Amenorrhoea (G3/4: 
NA) 

  

General disorders and 
administration site 
conditions 

Asthenia (G3/4: 
10.0%); 
Pyrexia (G3/4: NA); 
Oedema peripheral 
(G3/4: 0.2%) 

  

Investigations  Weight increased (G3/4: 
0%); 
Weight decreased 
(G3/4: 0.2%)

 

 
Description of selected of adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer 
 
Nervous system disorders 
In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 
the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 
of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 
observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 
In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 
persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 
arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 
sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 
(0.2%) in FAC arm. 
 
Cardiac disorders 
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 
congestive heart failure during the follow-up period. At the end of the follow-up period (actual median 
follow-up time of 10 years and 5 months), no patients  had CHF in TAC arm and 1 patient in TAC arm 
died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient (0.2%) in 
FAC arm. 
 
Skin and subcutaneous tissue disorders 
In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 
At the end of the follow-up period (actual median follow-up time of	8 years), alopecia was observed to 
be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-
up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 
FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 
42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 
period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 
patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.  
   
Reproductive system and breast disorders 
In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 



71 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 
(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 
In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 
follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 
in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 
amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 
FAC arm. 
 
General disorders and administration site conditions 
In study TAX316 peripheral oedema that started during the treatment period and persisted into the 
follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 
23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 
years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  
In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-
up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 
FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 
lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 
In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 
FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 
asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
 
In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 
follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 
the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 
had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 
Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 
(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 
lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 
FAC arm.  
Asthenia that started during the treatment period and persisted into the follow-up period was observed 
to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 
follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 
patients (0.4%) in FAC arm. 
 
Acute leukaemia / Myelodysplastic syndrome. 
After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 
(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 
syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%).  
After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 
patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 
myelodysplastic syndrome in either treatment groups. 
 
Neutropenic complications 
Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 
infection was decreased in patients who received primary G-CSF prophylaxis after it was made 
mandatory in the TAC arm – GEICAM study.  
 
Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 
(GEICAM 9805) 
 
 Without primary 

G-CSF prophylaxis 
(n = 111) 

n (%) 

With primary  
G-CSF prophylaxis 

(n = 421)  
n (%) 



72 

Neutropenia (Grade 4)  104 (93.7) 135 (32.1) 
 

Febrile neutropenia  28 (25.2) 23 (5.5) 
 

Neutropenic infection  14 (12.6) 21 (5.0) 
 

Neutropenic infection 
(Grade 3-4)  

2 (1.8) 5 (1.2) 

 
Tabulated list of adverse reactions in gastric adenocarcinoma cancer for Docetaxel Zentiva 75 mg/m² 
in combination with cisplatin and 5-fluorouracil 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Neutropenic infection; 
Infection (G3/4: 11.7%)

 

Blood and lymphatic system 
disorders 

Anaemia (G3/4: 20.9%); 
Neutropenia (G3/4: 83.2%);  
Thrombocytopenia (G3/4: 
8.8%); 
Febrile neutropenia 

 

Immune system disorders Hypersensitivity (G3/4: 1.7%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 11.7%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%);  
Peripheral motor neuropathy 
(G3/4: 1.3%) 

Eye disorders  Lacrimation increased (G3/4: 
0%)

Ear and labyrinth disorders  Hearing impaired (G3/4: 0%)
Cardiac disorders  Arrhythmia (G3/4: 1.0%) 
Gastrointestinal disorders Diarrhoea (G3/4: 19.7%);  

Nausea (G3/4: 16%);  
Stomatitis (G3/4: 23.7%); 
Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 
Gastrointestinal pain (G3/4: 
1.0%); 
Oesophagitis/dysphagia/odynop
hagia (G3/4: 0.7%) 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%);  
Nail disorders (G3/4: 0.7%);  
Skin exfoliation (G3/4: 0%)

General disorders and 
administration site conditions 

Lethargy (G3/4: 19.0%); 
Fever (G3/4: 2.3%); 
Fluid retention 
(severe/life-threatening: 1%)

 

 
Description of selected adverse reactions in gastric adenocarcinoma cancer for Docetaxel 
Zentiva 75 mg/m2 in combination with ciplatin and 5-fluorouracil 
 
Blood and lymphatic system disorders 
Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 
regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 
the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 
patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 
prophylactic G-CSF (see section 4.2). 
 



73 

Tabulated list of adverse reactions in head and neck cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin and 5-fluorouracil 
 
 Induction chemotherapy followed by radiotherapy (TAX 323) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 6.3%); 
Neutropenic infection

  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
0.6%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
76.3%); 
Anaemia (G3/4: 9.2%); 
Thrombocytopenia 
(G3/4: 5.2%) 

Febrile neutropenia  

Immune system 
disorders 

 Hypersensitivity (no 
severe)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 0.6%)   

Nervous system 
disorders 

Dysgeusia/Parosmia; 
Peripheral sensory 
neuropathy (G3/4: 
0.6%) 

Dizziness  

Eye disorders  Lacrimation increased; 
Conjunctivitis 

 

Ear and labyrinth 
disorders 

 Hearing impaired  

Cardiac disorders  Myocardial ischemia 
(G3/4:1.7%)

Arrhythmia (G3/4: 
0.6%) 

Vascular disorders  Venous disorder (G3/4: 
0.6%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 0.6%); 
Stomatitis (G3/4: 
4.0%); 
Diarrhoea (G3/4: 2.9%);
Vomiting (G3/4: 0.6%) 

Constipation; 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
0.6%); 
Abdominal pain; 
Dyspepsia; 
Gastrointestinal 
haemorrhage (G3/4: 
0.6%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 
Dry skin;  
Skin exfoliative (G3/4: 
0.6%)

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.6%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 3.4%); 
Pyrexia (G3/4: 0.6%); 
Fluid retention; 
Oedema 

  

Investigations  Weight increased



74 

 
 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 3.6%) 
 

Neutropenic infection  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
1.2%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
83.5%); 
Anaemia (G3/4: 
12.4%); 
Thrombocytopenia 
(G3/4: 4.0%); 
Febrile neutropenia

  

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 
12.0%) 

  

Nervous system 
disorders 

Dysgeusia/Parosmia 
(G3/4: 0.4%); 
Peripheral sensory 
neuropathy (G3/4: 
1.2%) 

Dizziness (G3/4: 
2.0%); 
Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
2.0%)

Ischemia myocardial 

Vascular disorders  Venous disorder
Gastrointestinal 
disorders 

Nausea (G3/4: 13.9%); 
Stomatitis (G3/4: 
20.7%); 
Vomiting (G3/4: 
8.4%); 
Diarrhoea (G3/4: 
6.8%); 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
12.0%); 
Constipation (G3/4: 
0.4%) 

Dyspepsia (G3/4: 
0.8%); 
Gastrointestinal pain 
(G3/4: 1.2%); 
Gastrointestinal 
haemorrhage (G3/4: 
0.4%) 
 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 4.0%); 
Rash pruritic 

Dry skin ; 
Desquamation

 

Musculoskeletal, 
connective tissue bone 
disorders 

 Myalgia (G3/4: 0.4%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 4.0%); 
Pyrexia (G3/4: 3.6%); 
Fluid retention (G3/4: 
1.2%); 
Oedema (G3/4: 1.2%)

  



75 

MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Investigations Weight decreased Weight increased
 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 
Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 
reported in association with docetaxel when used in combination with other anticancer treatments 
known to be associated with second primary malignancies. Acute myeloid leukaemia and 
myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 
breast cancer with TAC regimen. 
 
Blood and lymphatic system disorders 
Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been 
reported. 
 
Immune system disorders 
Some cases of anaphylactic shock, sometimes fatal, have been reported.  
Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 
previously experienced hypersensitivity reactions to paclitaxel. 
 
Nervous system disorders 
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 
administration. These reactions sometimes appear during the infusion of the medicinal product. 
 
Eye disorders 
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 
during infusion of the medicinal product and in association with hypersensitivity reactions have been 
reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 
without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 
rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 
docetaxel. 
 
Ear and labyrinth disorders 
Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 
 
Cardiac disorders 
Rare cases of myocardial infarction have been reported. 
Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 
been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-
fluorouracil and/ or cyclophosphamide. 
 
Vascular disorders 
Venous thromboembolic events have rarely been reported. 
 
Respiratory, thoracic and mediastinal disorders 
Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.  
 
Gastrointestinal disorders 
Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 
reported with a potential fatal outcome (frequency not known). 



76 

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 
including enterocolitis and gastrointestinal perforation.  
Rare cases of ileus and intestinal obstruction have been reported. 
 
Hepatobiliary disorders 
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 
 
Skin and subcutaneous tissue disorders  
Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 
cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 
(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel. 
Sclerodermal-like changes usually preceded by peripheral lymphoedema have been reported with 
docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 
 
Renal and urinary disorders 
Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 
risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and gastro-
intestinal disorders. 
 
General disorders and administration site conditions 
Radiation recall phenomena have rarely been reported. 
Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 
administration of docetaxel at a different site) has been observed at the site of previous extravasation 
(frequency not known). 
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 
 
Metabolism and nutrition disorders 
Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 
mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 
hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 
with diarrhoea. 
 
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 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Taxanes, ATC Code: L01CD02 
 



77 

Mechanism of action 
 
Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 
microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 
binding of docetaxel to microtubules does not alter the number of protofilaments. 
 
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 
vital mitotic and interphase cellular functions.  
 
Pharmacodynamic effects 
 
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 
against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 
concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 
but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 
gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour 
activity against advanced murine and human grafted tumours. 
 
Clinical efficacy and safety 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide: adjuvant therapy 
 
Patients with operable node-positive breast cancer (TAX 316) 
 
Data from a multi-centre open label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS  80%, between 18 and 
70 years of age. After stratification according to the number of positive lymph nodes (1-3, 4+), 
1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 
doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 
followed by fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 (FAC arm). Both regimens 
were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 
all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 
secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 
prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 
ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 
both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 
receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 
according to guidelines in place at participating institutions and was given to 69% of patients who 
received TAC and 72% of patients who received FAC.  
Two interim analyses and one final analysis were performed. The first interim analysis was planned 3 
years after the date when half of study enrolment was done. The second interim analysis was done 
after 400 DFS events had been recorded overall, which led to a median follow-up of 55 months. The 
final analysis was performed when all patients had reached their 10-year follow-up visit (unless they 
had a DFS event or were lost to follow-up before). Disease-free survival (DFS) was the primary 
efficacy endpoint and overall survival (OS) was the secondary efficacy endpoint. 
 
A final analysis was performed with an actual median follow-up of 96 months. Significantly longer 
disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 
relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 
(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 
10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 
i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 
with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 
in patients with 4+ nodes was not fully demonstrated at the final analysis. 
  



78 

 
Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analysed: 
 
  Disease free survival Overall survival 
Patient subset Number 

of 
patients 

Hazard 
ratio* 

95% CI p = Hazard 
ratio* 

95% CI p = 

No of positive 
nodes 

       

Overall 745 0.80 0.68-0.93 0.0043 0.74 0.61-0.90 0.0020 
1-3 467 0.72 0.58-0.91 0.0047 0.62 0.46-0.82 0.0008
4+ 278 0.87 0.70-1.09 0.2290 0.87 0.67-1.12 0.2746
*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 
overall survival compared to FAC 
 
Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805)  
 
Data from a multi-centre open label randomised trial support the use of Docetaxel Zentiva for the 
adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 
chemotherapy. 1060 patients were randomised to receive either Docetaxel Zentiva 75 mg/m2 
administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 
TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclophosphamide 
500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 
patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size >2 cm and/or 
negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age <35 years). Both 
regimens were administered once every 3 weeks for 6 cycles. Docetaxel Zentiva was administered as a 
1-hour infusion, all other medicinal products were given intravenously on day 1 every three weeks. 
Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients were randomised. 
The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection was decreased in 
patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, after the last cycle 
of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 20 mg once a day for 
up to 5 years. Adjuvant radiation therapy was administered according to guidelines in place at 
participating institutions and was given to 57.3% of patients who received TAC and 51.2% of patients 
who received FAC. 
 
One primary analysis and one updated analysis were performed. The primary analysis was done when 
all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 
analysis was performed when all patients had reached their 10-year (median follow up time of 10 
years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 
previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 
was the secondary efficacy endpoint. 
 
At the median follow-up time of 77 months, significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). At the 
median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% reduction in the 
risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 
p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 
favour of TAC.   
 
At the median follow-up time of 77 months, overall survival (OS) was longer in the TAC arm with 
TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard 
ratio = 0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly 
different between the 2 groups. 



79 

At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 
the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  
The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 
point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 
 
The positive benefit risk ratio for TAC compared to FAC remained unchanged.   
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 
in the primary analysis (at the median follow-up time of 77 months) (see table below): 
 



80 

 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study  
(Intent-to-Treat Analysis) 

 
  Disease Free Survival 
Patient subset Number of patients 

in TAC group 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1  
<50 years 260 0.67 0.43-1.05 
≥50 years 279 0.67 0.43-1.05 
Age category 2  
<35 years 42 0.31 0.11-0.89 
≥35 years 497 0.73 0.52-1.01 
Hormonal receptor 
status 

   

Negative 195 0.7 0.45-1.1 
Positive 344 0.62 0.4-0.97 
Tumour size   
2 cm 285 0.69 0.43-1.1 
>2 cm 254 0.68 0.45-1.04 
Histological grade  
Grade1 (includes grade 
not assessed) 

64 0.79 0.24-2.6 

Grade 2 216 0.77 0.46-1.3 
Grade 3 259 0.59 0.39-0.9 
Menopausal status  
Pre-Menopausal 285 0.64 0.40-1 
Post-Menopausal 254 0.72 0.47-1.12 

*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 
survival compared to FAC. 

 
Exploratory subgroup analyses for  disease-free survival for  patients who meet the 2009 St. Gallen 
chemotherapy criteria – (ITT population) were performed and presented here below: 
 
  

TAC 
 

FAC 
Hazard ratio 
(TAC/FAC) 

 
 

Subgroups (n=539) (n=521) (95% CI) p-value
 
Meeting relative indication 
for chemotherapy a 

    

 
No 

 
18/214 
(8.4%)

 
26/227 
(11.5%)

 
0.796 (0.434 - 1.459) 

 
0.4593 

 
Yes 

 
48/325 
(14.8%)

 
69/294 
(23.5%)

 
0.606 (0.42 - 0.877) 

 
0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 
FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 
CI = confidence interval 
ER = oestrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 



81 

Docetaxel Zentiva as single agent 
 
Two randomised phase III comparative studies, involving a total of 326 alkylating or 
392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 
recommended dose and regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 
time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 
response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 
p = 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 
15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 
failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 
(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p = 0.0004) and 
prolonged overall survival (11 months vs. 9 months, p = 0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 
observed in phase II studies (see section 4.8).  
 
An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 
therapy should have included an anthracycline. A total of 449 patients were randomised to receive 
either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 
infusion. Both regimens were administered every 3 weeks. 
Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 
prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 
(15.3 months vs 12.7 months; p = 0.03). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%).  
 
Docetaxel Zentiva in combination with doxorubicin 
 
One large randomised phase III study, involving 429 previously untreated patients with metastatic 
disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 
(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) 
(AC arm). Both regimens were administered on day 1 every 3 weeks. 
 
 Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 
27.4 - 36.0) in AC arm. 
 Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC arm. 
 
In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 
neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 
(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 
higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 
incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 
decrease  20% (13.1% versus 6.1%), absolute LVEF decrease  30% (6.2% versus 1.1%). Toxic 
deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 
(1 due to septic shock and 3 due to congestive heart failure). 
In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 
treatment and follow-up. 
 



82 

Docetaxel Zentiva in combination with trastuzumab 
 
Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 
breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 
for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 
(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 
chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 
received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 
this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 
fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 
and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 
summarized in the following table: 
 

Parameter Docetaxel plus trastuzumab1 
n = 92

Docetaxel1 
n = 94 

Response rate  
(95% CI) 

61% 
(50-71)

34% 
(25-45) 

Median duration of response 
(months) 
(95% CI) 

 
11.4 

(9.2-15.0)

 
5.1 

(4.4-6.2) 
Median TTP (months) 
(95% CI) 

10.6 
(7.6-12.9)

5.7 
(5.0-6.5) 

Median survival (months) 
(95% CI) 

30.52 
(26.8-ne)

22.12 
(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached. 
1Full analysis set (intent-to-treat) 
2 Estimated median survival 

 
Docetaxel Zentiva in combination with capecitabine 
 
Data from one multi-centre, randomised, controlled phase III clinical study support the use of 
docetaxel in combination with capecitabine for treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 
study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 
infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 
rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 
intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 
combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 
(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 
assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 
progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 
median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 
 
Non-small cell lung cancer 
 
Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 
and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 
Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 
There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 
disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 
docetaxel at 75 mg/m² compared to those with BSC. 
The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 
26.1 weeks. 
 



83 

Docetaxel Zentiva in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 
administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 
day 1 of cycles repeated every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated 
in the following table: 
 
 TCis 

n = 408
VCis 

n = 404
Statistical analysis 

Overall survival  
(Primary end-point): 

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 
[97.2% CI: 0.937; 1.342]* 

1-year Survival (%) 46 41 Treatment difference: 5.4% 
[95% CI: -1.1; 12.0] 

2-year Survival (%) 21 14 Treatment difference: 6.2% 
[95% CI: 0.2; 12.3] 

Median time to progression 
(weeks): 

 
22.0 

 
23.0 

 
Hazard Ratio: 1.032 

[95% CI: 0.876; 1.216] 
Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 
*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 
region of treatment), based on evaluable patient population. 
 
Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnofsky performance status. Results on these end-points 
were supportive of the primary end-points results.  
 
For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 
compared to the reference treatment combination VCis. 
 
Prostate cancer 
 
Metastatic castration-resistant prostate cancer 
 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with  
metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 
study (TAX 327). A total of 1006 patients with KPS  60 were randomised to the following treatment 
groups: 
 Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 
 Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 
 Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 
continuously. 
 
Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 
compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 
arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 
the docetaxel arms versus the control arm are summarized in the following table: 



84 

 
Endpoint 
 

Docetaxel  
every 3 weeks 

Docetaxel  
every week

Mitoxantrone  
every 3 weeks 

Number of patients 
Median survival (months) 
95% CI 
Hazard ratio 
95% CI 
p-value†* 

335 
18.9 

(17.0-21.2) 
0.761 

(0.619-0.936) 
0.0094

334 
17.4 

(15.7-19.0) 
0.912 

(0.747-1.113) 
0.3624

337 
16.5 

(14.4-18.6) 
-- 
-- 
-- 

Number of patients 
PSA** response rate (%) 
95% CI 
p-value* 

291 
45.4 

(39.5-51.3) 
0.0005

282 
47.9 

(41.9-53.9) 
<0.0001

300 
31.7 

(26.4-37.3) 
-- 

Number of patients 
Pain response rate (%) 
95% CI 
p-value* 

153 
34.6 

(27.1-42.7) 
0.0107

154 
31.2 

(24.0-39.1) 
0.0798

157 
21.7 

(15.5-28.9) 
-- 

Number of patients 
Tumour response rate (%) 
95% CI 
p-value* 

141 
12.1 

(7.2-18.6) 
0.1112 

134 
8.2 

(4.2-14.2) 
0.5853 

137 
6.6 

(3.0-12.1) 
-- 

†Stratified log rank test 
*Threshold for statistical significance = 0.0175 
**PSA: Prostate-Specific Antigen 
 
Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 
3 weeks, it is possible that certain patients may benefit from docetaxel every week. 
 
No statistical differences were observed between treatment groups for Global Quality of Life. 
 
Metastatic hormone-sensitive prostate cancer 
STAMPEDE study 
 
The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 
patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 
evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 
II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment armss of interest:  
 Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles    
 Standard of care alone  
Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 
continuously.  
Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 
docetaxel in combination with standard of care, 724 received standard of care alone.  
 
In these metastatic prostate cancer patients, the median overall survival was significantly longer in 
docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 
months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 
p=0.005).  
 
Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 
summarized in the following table: 
 



85 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 
treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 
 

Endpoint 
 

Docetaxel + standard of care 
 

Standard of care alone 

Number of metastatic prostate 
cancer patients 
 
Median overall survival (months)  
95% CI 

362 
 
 

62 
51-73 

724 
 
 

43 
40-48 

Adjusted hazard ratio 
95% CI 
p-valuea 

0.76 
(0.62-0.92) 

0.005 

Failure-Free survivalb    
Median (months) 
95% CI 

20.4 
16.8-25.2

12 
9.6-12 

Adjusted hazard ratio 
95% CI 
p-valuea 

0.66 
(0.57-0.76) 

< 0.001 
a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 
(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 
failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 
and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 
metastases; skeletal-related event; or death from prostate cancer. 
 

 
CHAARTED study 
 
The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 
(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 
Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 
treatment groups.  

 ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 
for 6 cycles 

 ADT alone   
 
The median overall survival was significantly longer in docetaxel treatment group than in the ADT 
alone group, with a median overall survival 13.6 months  longer with the addition of docetaxel to ADT 
(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  
 
Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 
 



86 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 
cancer (CHAARTED) 
 

Endpoint 
 

Docetaxel +ADT  
 

ADT alone 

Number of patients 
Median overall survival (months) 
All patients 
95% CIAdjusted hazard ratio 

397 
 

57.6 
49.1-72.8 

0.61

393 
 

44.0 
34.4-49.1 

--
95% CI (0.47-0.80)  --
p-valuea 0.0003 -- 
Progression Free Survival 
Median (months) 
95% CI 
Adjusted hazard ratio 
95% CI 
p-value* 

 
19.8 

16.7-22.8 
0.60 

0.51-0.72 
P<0.0001 

 
11.6 

10.8-14.3 
-- 
-- 
-- 

PSA response** at 6 months – N(%) 
p-valuea* 

127 (32.0) 
<0.0001 

77 (19.6) 
-- 

PSA response** at 12 months – N(%) 
p-valuea* 

110 (27.7) 
<0.0001 

66 (16.8) 
-- 

Time to castration-resistant prostate cancerb   
Median (months)  
95% CI 
Adjusted hazard ratio 

20.2 
(17.2-23.6) 

0.61 

11.7 
(10.8-14.7) 

-- 
95% CI (0.51-0.72) --
p-valuea* <0.0001 -- 

Time to clinical progressionc    
Median (months)  33.0 19.8
95% CI (27.3-41.2) (17.9-22.8)
Adjusted hazard ratio 0.61 -- 
95% CI (0.50-0.75) --
p-valuea* <0.0001 -- 
a Time to event variables: Stratified log-rank test.  
  Response rate variables: Fisher's Exact test  
* p-value for descriptive purpose. 
** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 
consecutive measurements at least 4 weeks apart. 
b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 
clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 
Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 
per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 
increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 
due to cancer according to the investigator’s opinion).
 
Gastric adenocarcinoma 
 
A multi-centre, open-label, randomised study was conducted to evaluate the safety and efficacy of 
docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 
adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 
metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 



87 

(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 
(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 
day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 
arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 
arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 
endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 
TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 
(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 
summarized in the following table: 
 
Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 
Endpoint TCF 

n = 221
CF 

n = 224
Median TTP (months) 5.6 3.7 
(95% CI) (4.86-5.91) (3.45-4.47) 
Hazard ratio 1.473 
(95% CI) (1.189-1.825) 
*p-value 0.0004 
Median survival (months) 9.2 8.6 
(95% CI) (8.38-10.58) (7.16-9.46)
2-year estimate (%) 18.4 8.8 
Hazard ratio 1.293 
(95% CI) (1.041-1.606) 
*p-value 0.0201 
Overall response rate (CR+PR) (%) 36.7 25.4 
p-value 0.0106 
Progressive disease as best overall response (%) 16.7 25.9 

*Unstratified log rank test 
 
Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 
arm. 
 
A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 
a statistically significant difference although always in favour of the TCF regimen and showed that the 
benefit of TCF over CF is clearly observed between 18 and 30 months of follow up. 
 
Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 
of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 
health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 
Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 
 
Head and neck cancer 
 
 Induction chemotherapy followed by radiotherapy (TAX323) 
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 
carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 
randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO perfomance status 0 or 1, were randomised to one of two treatment arms. Patients on the 
docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 
5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 
administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 
bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 
a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 
progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 
Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 
1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 



88 

at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 
after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 
of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 
institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 
with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 
70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 
interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 
regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 
chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 
with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 
The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 
TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 
overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 
favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 
28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below: 
 
Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 
(Intent-to-Treat Analysis) 
 

Endpoint Docetaxel + 
Cis + 5-FU 

n = 177 

Cis + 5-FU 
 

n = 181 
Median progression free survival (months) 
(95% CI) 

11.4 
(10.1-14.0)

8.3 
(7.4-9.1)

Adjusted hazard ratio 
(95% CI) 
*p-value 

0.70 
(0.55-0.89) 

0.0042 
Median survival (months) 
(95% CI) 

18.6 
(15.7-24.0)

14.5 
(11.6-18.7)

Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95% CI) 

67.8 
(60.4-74.6)

53.6 
(46.0-61.0)

***p-value 0.006 
Best overall response to study treatment 
[chemotherapy +/- radiotherapy] (%) 
(95% CI) 

 
72.3 

(65.1-78.8)

 
58.6 

(51.0-65.8)
***p-value 0.006 
Median duration of response to chemotherapy  
radiotherapy (months) 
(95% CI) 

n = 128 
15.7 

(13.4-24.6) 

n = 106 
11.7 

(10.2-17.4) 
Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.52-0.99) 

0.0457 
A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 
**Log rank test 
*** Chi-square test 

 
Quality of life parameters 
 
Patients treated with TPF experienced significantly less deterioration of their Global health score 
compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale).  
 
Clinical benefit parameters 
 



89 

The performance status scale, for head and neck (PSS-HN) subscales designed to measure 
understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 
of TPF as compared to PF. 
Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 
compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 
pain management. 
 
 Induction chemotherapy followed by chemoradiotherapy (TAX324) 
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 
squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 
open-label, phase III study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 
a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 
comprised patients with technically unresectable disease, patients with low probability of surgical cure 
and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 
endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 
arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 
100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 
intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 
repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 
chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 
cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 
continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 
were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 
receive CRT as per protocol (PF/CRT).  
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 
with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 
day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 
intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 
using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 
70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at any time 
following completion of CRT. All patients on the docetaxel-containing arm of the study received 
prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 
significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 
(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 
to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 
follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 
progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 
PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 
p = 0.004. Efficacy results are presented in the table below: 
 



90 

Efficacy of docetaxel in the induction treatment of patients with locally advanced SCCHN (Intent-to-
Treat Analysis) 
 

Endpoint Docetaxel + Cis + 5-FU 
n = 255 

Cis + 5-FU 
n = 246 

Median overall survival (months)  
(95% CI) 

70.6 
(49.0-NA)

30.1 
(20.9-51.5) 

Hazard ratio: 
(95% CI) 
*p-value  

0.70 
(0.54-0.90) 

0.0058
Median PFS (months)  
(95% CI) 

35.5 
(19.3-NA)

13.1 
(10.6 - 20.2) 

Hazard ratio: 
(95% CI) 
**p-value  

0.71 
(0.56 - 0.90) 

0.004
Best overall response (CR + PR) to 
chemotherapy (%) 
(95% CI) 

71.8 
(65.8-77.2) 

64.2 
(57.9-70.2) 

***p-value 0.070
Best overall response (CR + PR) to study 
treatment [chemotherapy +/- 
chemoradiotherapy] (%) 
(95%CI) 

76.5 
(70.8-81.5) 

71.5 
(65.5-77.1) 

***p-value 0.209
A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil 
*un-adjusted log-rank test 
**un-adjusted log-rank test, not adjusted for multiple comparisons 
***Chi square test, not adjusted for multiple comparisons 
NA-not applicable 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Docetaxel Zentiva in all subsets of the paediatric population in breast cancer, non-small cell lung 
cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less 
differentiated nasopharyngeal carcinoma (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 
20-115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent 
with a three-compartment pharmacokinetic model with half-lives for the ,  and  phases of 4 min, 
36 min and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel 
from the peripheral compartment.  
 
Distribution 
 
Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 
level of 3.7 µg/ml was obtained with a corresponding AUC of 4.6 h.µg/ml. Mean values for total body 
clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 
individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 
bound to plasma proteins. 
 



91 

Elimination 
 
A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 
both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 
ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 
the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 
excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 
and very low amounts of unchanged medicinal product. 
 
Special populations 
 
Age and gender 
A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 
Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 
studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient. 
 
Hepatic impairment 
In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 
function impairment (ALT, AST  1.5 times the ULN associated with alkaline phosphatase 
 2.5 times the ULN), total clearance was lowered by 27% on average (see section 4.2). 
 
Fluid retention 
Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 
no data available in patients with severe fluid retention. 
 
Combination therapy 
 
Doxorubicin 
When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 
levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 
and cyclophosphamide were not influenced by their co-administration. 
 
Capecitabine 
Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 
showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 
effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5’-DFUR. 
 
Cisplatin 
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 
similar to that observed with cisplatin alone. 
 
Cisplatin and 5-fluorouracil 
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 
tumours had no influence on the pharmacokinetics of each individual medicinal product. 
 
Prednisone and dexamethasone 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 
dexamethasone premedication has been studied in 42 patients.  
 
Prednisone 
No effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
5.3 Preclinical safety data 
 
The carcinogenic potential of docetaxel has not been studied. 
 



92 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 
test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 
mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 
with the pharmacological activity of docetaxel. 
 
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair 
male fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polysorbate 80 
Ethanol anhydrous 
Citric acid 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf-life 
 
Unopened vial 
3 years 
 
After opening of the vial 
Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user.  
 
Once added to the infusion bag  
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions and the medicinal product should be used immediately. If not used immediately, in-use 
storage times and conditions are the responsibility of the user. 
 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 
25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 
intravenous administration).  
 
In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 
has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded.  
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Store in the original package in order to protect from light. 
 
For storage conditions of the diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
7 ml clear glass (type I) vial with a magenta aluminium seal and a magenta plastic flip-off cap 
containing 4 ml of concentrate. 



93 

 
Each box contains one vial. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Zentiva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Zentiva solutions. The use of gloves is 
recommended. 
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If Docetaxel Zentiva concentrate or infusion 
solution should come into contact with mucous membranes, wash immediately and thoroughly with 
water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion, 
which contains only 1 vial). 
 
Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution. 
 
Each vial is of single use and should be used immediately. 
 
If the vials are stored under refrigeration, allow the required number of boxes of Docetaxel Zentiva 
concentrate for solution for infusion to stand below 25°C for 5 minutes before use. 
More than one vial of Docetaxel Zentiva concentrate for solution for infusion may be necessary to 
obtain the required dose for the patient. Aseptically withdraw the required amount of Docetaxel 
Zentiva concentrate for solution for infusion using a calibrated syringe fitted with a 21G needle. 
 
In Docetaxel Zentiva 80 mg /4 ml vial the concentration of docetaxel is 20 mg/ml. 
The required volume of Docetaxel Zentiva concentrate for solution for infusion must be injected via a 
single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose solution 
or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 
that a concentration of 0.74 mg/ml docetaxel is not exceeded.  
 
Mix the infusion bag or bottle manually using a rocking motion. 
 
The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 
to the patient. 
As with all parenteral products, Docetaxel Zentiva infusion solution should be visually inspected prior 
to use, solutions containing a precipitate should be discarded. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
 Zentiva k.s., U kabelovny 130, 102 37 Prague 10, Czech Republic 
 



94 

8. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 April 2007 
Date of latest renewal: 20 April 2012 
 
 
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.  
 



95 

1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Zentiva 160 mg/8 ml concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate contains 20 mg docetaxel (as trihydrate). 
 
One vial of 8 ml of concentrate contains 160 mg of docetaxel. 
 
Excipient with known effect: 
Each vial of concentrate contains 4 ml of ethanol anhydrous (3.16 g).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is a pale yellow to brownish-yellow solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide is indicated for the 
adjuvant treatment of patients with: 

 operable node-positive breast cancer 
 operable node-negative breast cancer  

 
For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to 
patients eligible to receive chemotherapy according to internationally established criteria for primary 
therapy of early breast cancer (see section 5.1). 
Docetaxel Zentiva in combination with doxorubicin is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for 
this condition. 
 
Docetaxel Zentiva monotherapy is indicated for the treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have 
included an anthracycline or an alkylating agent. 
 
Docetaxel Zentiva in combination with trastuzumab is indicated for the treatment of patients with 
metastatic breast cancer whose tumours over express HER2 and who previously have not received 
chemotherapy for metastatic disease. 
 
Docetaxel Zentiva in combination with capecitabine is indicated for the treatment of patients with 
locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy 
should have included an anthracycline. 
 



96 

Non-small cell lung cancer 
 
Docetaxel Zentiva is indicated for the treatment of patients with locally advanced or metastatic non-
small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Zentiva in combination with cisplatin is indicated for the treatment of patients with 
unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 
previously received chemotherapy for this condition. 
 
Prostate cancer 
 
Docetaxel Zentiva in combination with prednisone or prednisolone is indicated for the treatment of 
patients with  metastatic castration-resistant prostate cancer. 
 
Docetaxel Zentiva in combination with androgen-deprivation therapy (ADT), with or without 
prednisone or prednisolone, is indicated for the treatment of patients with metastatic hormone-
sensitive prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of 
patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal 
junction, who have not received prior chemotherapy for metastatic disease. 
 
Head and neck cancer 
 
Docetaxel Zentiva in combination with cisplatin and 5-fluorouracil is indicated for the induction 
treatment of patients with locally advanced squamous cell carcinoma of the head and neck. 
 
4.2 Posology and method of administration 
 
The use of docetaxel should be confined to units specialised in the administration of cytotoxic 
chemotherapy and it should only be administered under the supervision of a physician qualified in the 
use of anticancer chemotherapy (see section 6.6). 
 
Posology 
 
For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 
corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 
docetaxel administration, unless contraindicated, can be used (see section 4.4).  
For metastatic castration-resistant prostate cancer, given the concurrent use of prednisone or 
prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours 
and 1 hour before the docetaxel infusion (see section 4.4). 
For metastatic hormone-sensitive prostate cancer, irrespective of the concurrent use of prednisone or 
prednisolone, the recommended premedication regimen is oral dexamethasone 8 mg 12 hours, 3 hours, 
and 1 hour before docetaxel infusion (see section 4.4). 
 
Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. 
 
Docetaxel is administered as a one-hour infusion every three weeks. 
 
Breast cancer 
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended 
dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 
500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment).  



97 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 
combination therapy with doxorubicin (50 mg/m2).  
 
In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 
with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 
the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 
immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 
well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 
characteristics. 
 
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, 
see capecitabine summary of product characteristics. 
 
Non-small cell lung cancer 
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen 
is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 
after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 
agent. 
 
Prostate cancer  
Metastatic castration-resistant prostate cancer  
The recommended dose of docetaxel is 75 mg/m2. Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
Metastatic hormone-sensitive prostate cancer 
The recommended dose of docetaxel is 75 mg/m2 every 3 weeks for 6 cycles. Prednisone or 
prednisolone 5 mg orally twice daily may be administered continuously. 
 
Gastric adenocarcinoma 
The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 
75 mg/m2, as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per 
day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. 
Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and 
appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the 
risk of haematological toxicities (see also Dose adjustments during treatment). 
 
Head and neck cancer 
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after 
cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological 
toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received 
prophylactic antibiotics. 
 
 Induction chemotherapy followed by radiotherapy (TAX 323) 

For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head 
and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour infusion 
followed by cisplatin 75 mg/m2 over 1 hour, on day one, followed by 5-fluorouracil as a 
continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 
3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.  

 
 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 

For the induction treatment of patients with locally advanced (technically unresectable, low 
probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the 
head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1 hour intravenous 
infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour 



98 

infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. 
This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should 
receive chemoradiotherapy. 

 
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product 
characteristics. 
 
Dose adjustments during treatment 
 
General  
Docetaxel should be administered when the neutrophil count is  1,500 cells/mm3.  
In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than 
one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel 
therapy, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 
60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be 
discontinued.  
 
Adjuvant therapy for breast cancer 
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 
cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 
neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all 
subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 
have their dose decreased to 60 mg/m². 
 
In combination with cisplatin 
For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 
nadir of platelet count during the previous course of therapy is < 25,000 cells/mm3, or in patients who 
experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 
dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 
corresponding summary of product characteristics. 
 
In combination with capecitabine 
 For capecitabine dose modifications, see capecitabine summary of product characteristics. 
 For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 

next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 
100% of the original dose.  

 For patients developing the second appearance of Grade 2 toxicity, or the first appearance of 
Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1 
and then resume treatment with docetaxel 55 mg/m².  

 For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel 
dose. 

 
For trastuzumab dose modifications, see trastuzumab summary of product characteristics. 
 
In combination with cisplatin and 5-fluorouracil 
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite 
G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of 
complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m2. In case of 
Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m2. Patients should 
not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level 
> 1,500 cells/mm3 and platelets recover to a level > 100,000 cells/mm3. Discontinue treatment if these 
toxicities persist (see section 4.4). 
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with 
cisplatin and 5-fluorouracil (5-FU): 
 

Toxicity Dose adjustment 
Diarrhoea grade 3  First episode: reduce 5-FU dose by 20%.



99 

Second episode: then reduce docetaxel dose by 20%.
Diarrhoea grade 4 First episode: reduce docetaxel and 5-FU doses by 20%. 

Second episode: discontinue treatment.
Stomatitis/mucositis 
grade 3  

First episode: reduce 5-FU dose by 20%. 
Second episode: stop 5-FU only, at all subsequent cycles. 
Third episode: reduce docetaxel dose by 20%.

Stomatitis/mucositis 
grade 4 

First episode: stop 5-FU only, at all subsequent cycles. 
Second episode: reduce docetaxel dose by 20%.

 
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product 
characteristics. 
 
In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged 
neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide 
prophylactic coverage (eg, day 6-15) in all subsequent cycles. 
 
Special populations 
 
Patients with hepatic impairment 
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both 
elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal 
range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of 
docetaxel is 75 mg/m2 (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or 
ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-
reduction can be recommended and docetaxel should not be used unless strictly indicated.  
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Paediatric population 
The safety and efficacy of Docetaxel Zentiva in nasopharyngeal carcinoma in children aged 1 month 
to less than 18 years have not yet been established. 
There is no relevant use of Docetaxel Zentiva in the paediatric population in the indications breast 
cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not 
including type II and III less differentiated nasopharyngeal carcinoma.  
 
Older people  
Based on a population pharmacokinetic analysis, there are no special instructions for use in the older 
people. 
In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 
capecitabine to 75% is recommended (see capecitabine summary of product characteristics). 
 
Method of administration 
For instructions on preparation and administration of the product, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Patients with baseline neutrophil count of < 1,500 cells/mm3. 
 
Patients with severe liver impairment (see sections 4.2 and 4.4). 
 
Contraindications for other medicinal products also apply, when combined with docetaxel. 



100 

 
4.4 Special warnings and precautions for use 
 
For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 
dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 
administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 
as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 
dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2).  
 
Haematology 
 
Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 
of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 
complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 
retreated with docetaxel when neutrophils recover to a level  1,500 cells/mm3 (see section 4.2). 
 
In the case of severe neutropenia (< 500 cells/mm3 for seven days or more) during a course of 
docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 
symptomatic measures are recommended (see section 4.2). 
 
In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 
neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 
G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 
complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 
Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 
 
In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 
febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 
primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 
adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 
neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 
closely monitored (see sections 4.2 and 4.8). 
 
Gastrointestinal reactions 

 
Caution is recommended for patients with neutropenia, particularly at risk for developing 
gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 
docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 
as on the first day of onset. Patients should be closely monitored for early manifestations of serious 
gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8). 
 
Hypersensitivity reactions 
 
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 docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. Patients who have previously experienced a 
hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 
including more severe hypersensitivity reaction. These patients should be closely monitored during 
initiation of docetaxel therapy. 
 
Cutaneous reactions 
 



101 

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 
followed by desquamation has been observed. Severe symptoms such as eruptions followed by 
desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 
section 4.2).  
 
Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic 
Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been 
reported with docetaxel treatment. Patients should be informed about the signs and symptoms of 
serious skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions 
appear, discontinuation of docetaxel should be considered. 
 
Fluid retention 
 
Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be 
monitored closely. 
 
Respiratory disorders 
 
Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, 
pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 
outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 
investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until 
diagnosis is available. Early use of supportive care measures may help improve the condition. The 
benefit of resuming docetaxel treatment must be carefully evaluated. 
 
Patients with liver impairment 
 
In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 
(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 
greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 
toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 
infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 
in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 
baseline and before each cycle (see section 4.2). 
For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent 
with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended 
and docetaxel should not be used unless strictly indicated. 
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no 
dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No 
data are available in patients with hepatic impairment treated by docetaxel in combination in the other 
indications. 
 
Patients with renal impairment 
 
There are no data available in patients with severely impaired renal function treated with docetaxel.  
 
Nervous system 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2). 
 



102 

Cardiac toxicity 
 
Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, 
particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may 
be moderate to severe and has been associated with death (see section 4.8). 
 
When patients are candidates for treatment with docetaxel in combination with trastuzumab, they 
should undergo baseline cardiac assessment. Cardiac function should be further monitored during 
treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 
more details see summary of product characteristics of trastuzumab. 
 
Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 
patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or 
cyclophosphamide (see section 4.8).  
Baseline cardiac assessment is recommended. 
 
Eye disorders 
 
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 
4.8). 
 
Second primary malignancies 
 
Second primary malignancies have been reported when docetaxel was given in combination with 
anticancer treatments known to be associated with second primary malignancies.  Second primary 
malignancies (including acute myeloid leukaemia, myelodysplastic syndrome and non-Hodgkin 
lymphoma) may occur several months or years after docetaxel-containing therapy. Patients should be 
monitored for second primary malignancies (see section 4.8). 
 
Others 
 
Contraceptive measures must be taken by both men and women during treatment and for men at least  
6 months after cessation of therapy (see section 4.6). 
 
The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 
clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 
voriconazole) should be avoided (see section 4.5). 
 
Additional cautions for use in adjuvant treatment of breast cancer 
 
Complicated neutropenia 
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 
 
Gastrointestinal reactions 
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 
 
Congestive heart failure (CHF) 
Patients should be monitored for symptoms of congestive heart failure during therapy and during the 
follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 
CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 
 
Patients with 4+ nodes 



103 

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 
nodes was not fully demontrated at the final analysis (see section 5.1). 
 
 
 
 
 
Elderly 
 
Cautions for use in adjuvant treatment of breast cancer 
There are limited data available in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Cautions for use in castration-resistant prostate cancer 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study (TAX 327), 
209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients 
treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate 
 10% higher in patients who were 65 years of age or greater compared to younger patients. The 
incidence of related fever, diarrhoea, anorexia, and peripheral oedema occurred at rates  10% higher 
in patients who were 75 years of age or greater versus less than 65 years. 
 
Cautions for use in hormone-sensitive prostate cancer 
Of the 545 patients treated with docetaxel every 3 weeks in a hormone-sensitive prostate cancer study 
(STAMPEDE), 296 patients were 65 years of age or older, and 48 patients were 75 years of age or 
older. More patients aged ≥65 years in the docetaxel arm reported hypersensitivity reaction, 
neutropenia, anemia, fluid retention, dyspnea, and nail changes when compared to the patients aged 
less than 65 years. None of these increases in frequency reached 10% difference with the control arm. 
In patients who were 75 years of age or older, when compared to younger patients, neutropenia, 
anemia, diarrhea, dyspnea and upper respiratory tract infection were reported with a greater incidence 
(at least 10% higher).  
 
Cautions for use in gastric adenocarcinoma cancer 
Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) 
patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer 
study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of 
serious adverse events was higher in the older people patients compared to younger patients. The 
incidence of the following adverse events (all grades): lethargy, stomatitis, neutropenic infection 
occurred at rates  10% higher in patients who were 65 years of age or older compared to younger 
patients.  
Older people patients treated with TCF should be closely monitored. 
 
Excipients 
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.16 g ethanol 
anhydrous  per vial, equivalent to 80 ml of beer or 33 ml wine. 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as 
patients with liver disease, or epilepsy. 
 
Consideration should be given to possible effects on the central nervous system. 
 



104 

4.5 Interaction with other medicinal products and other forms of interaction 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 
a result, caution should be exercised when treating patients with these medicinal products as 
concomitant therapy since there is a potential for a significant interaction. 
 
In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 
increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 
ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 
telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 
dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 
(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 
the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 
49%. 
Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 
prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 
No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal product has not been investigated formally, in vitro interactions 
with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 
phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 
docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 
influence the binding of digitoxin. 
 
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 
co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 
between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 
about 50% higher than values previously reported for carboplatin monotherapy. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 
both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other 
cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated. 
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
Breast-feeding 
 
Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 
Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 
discontinued for the duration of docetaxel therapy. 
 
Contraception in males and females  
 
An effective method of contraception should be used during treatment. 
 



105 

Fertility 
 
In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 
Therefore, men being treated with docetaxel 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.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. The amount of 
alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 
use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 
of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 
machines, and be advised not to drive or use machines if they experience these side effects during 
treatment. 
 
4.8 Undesirable effects 
 
Summary of the safety profile for all indications 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in:  

 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 
respectively. 

 258 patients who received docetaxel in combination with doxorubicin.  
 406 patients who received docetaxel in combination with cisplatin.  
 92 patients treated with docetaxel in combination with trastuzumab.  
 255 patients who received docetaxel in combination with capecitabine. 
 332 patients (TAX327) who received docetaxel in combination with prednisone or 

prednisolone (clinically important treatment related adverse events are presented). 
 1276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received 

docetaxel in combination with doxorubicin and cyclophosphamide (clinically important 
treatment related adverse events are presented). 

 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 
79 patients in the phase II part) who received docetaxel in combination with cisplatin and 
5-fluorouracil (clinically important treatment related adverse events are presented). 

 174 and 251 head and neck cancer patients who received docetaxel in combination with 
cisplatin and 5-fluorouracil (clinically important treatment related adverse events are 
presented). 

 545 patients (STAMPEDE study) who received docetaxel in combination with prednisone or 
prednisolone and ADT. 

 
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 
grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are 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 available 
data). 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 
reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 
neutropenia (< 500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 
and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 
combination with other chemotherapeutic agents. 
 



106 

For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 
was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 
trastuzumab combination arm compared to docetaxel monotherapy. 
 
For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 
reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 
capecitabine summary of product characteristics). 
 
For combination with ADT and with prednisone or prednisolone (STAMPEDE study), adverse events 
occurring over the 6 cycles of treatment with docetaxel and having at least 2% higher incidence in the 
docetaxel treatment arm by comparison to the control arm, are presented, using the CTCAE grading 
scale. 
 
 
The following adverse reactions are frequently observed with docetaxel: 
 
Immune system disorders 
 
Hypersensitivity reactions have generally occurred within a few minutes following the start of the 
infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 
were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. 
Severe reactions were characterised by hypotension and/or bronchospasm or generalized 
rash/erythema (see section 4.4). 
 
Nervous system disorders 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 
4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain 
including burning. Neuro-motor events are mainly characterised by weakness. 
 
Skin and subcutaneous tissue disorders 
 
Reversible cutaneous reactions have been observed and were generally considered as mild to 
moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 
hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 
associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 
Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 
interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 
nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis.  
 
General disorders and administration site conditions 
 
Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 
redness or dryness of the skin, phlebitis or extravasation and swelling of the vein. 
Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 
pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 
extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 
cumulative in incidence and severity (see section 4.4). 
 
Tabulated summary of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² single 
agent 
 
MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infections (G3/4: 5.7%; 
including sepsis and 

Infection associated 
with G4 neutropenia 

 



107 

MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

pneumonia, fatal in 
1.7%)  

(G3/4: 4.6%) 

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
76.4%);  
Anaemia (G3/4: 8.9%); 
Febrile neutropenia

Thrombocytopenia (G4: 
0.2%) 

 

Immune system 
disorders 

Hypersensitivity (G3/4: 
5.3%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 4.1%); 
Peripheral motor 
neuropathy (G3/4: 4%); 
Dysgeusia (severe: 
0.07%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension;  
Hypertension; 
Haemorrhage

 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe: 
2.7%) 

  

Gastrointestinal 
disorders 

Stomatitis (G3/4: 
5.3%);  
Diarrhoea (G3/4: 4%);  
Nausea (G3/4: 4%);  
Vomiting (G3/4: 3%) 

Constipation (severe: 
0.2%);  
Abdominal pain 
(severe: 1%);  
Gastrointestinal 
haemorrhage (severe: 
0.3%)

Oesophagitis (severe: 
0.4%) 

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Skin reaction (G3/4: 
5.9%);  
Nail disorders (severe: 
2.6%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 1.4%) Arthralgia  

General disorders and 
administration site 
conditions 

Fluid retention (severe: 
6.5%); 
Asthenia (severe: 
11.2%);  
Pain 

Infusion site reaction;  
Non-cardiac chest pain 
(severe: 0.4%) 

 

Investigations  G3/4 Blood bilirubin 
increased (< 5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 4%);  
G3/4 AST increased 
(< 3%); 
G3/4 ALT increased 
(< 2%)

 



108 

 
Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m2 single 
agent 
 
Blood and lymphatic system disorders 
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia. 
 
Nervous system disorders 
Reversibility data are available among 35.3% of patients who developed neurotoxicity following 
docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 
3 months. 
 
Skin and subcutaneous tissue disorders 
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 
were reversible within 21 days. 
 
General disorders and administration site conditions 
The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 
time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 
severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 
compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 
has been reported in some patients during the early courses of therapy. 
 
Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² 
single agent 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Infections (G3/4: 5%)
Blood and lymphatic system 
disorders 

Neutropenia (G4: 54.2%);  
Anaemia (G3/4: 10.8%); 
Thrombocytopenia (G4: 1.7%)

Febrile neutropenia 

Immune system disorders  Hypersensitivity (no severe)
Metabolism and nutrition 
disorders 

Anorexia  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 0.8%)

Peripheral motor neuropathy 
(G3/4: 2.5%) 

Cardiac disorders  Arrhythmia (no severe)  
Vascular disorders  Hypotension 
Gastrointestinal disorders Nausea (G3/4: 3.3%);  

Stomatitis (G3/4: 1.7%);  
Vomiting (G3/4: 0.8%);  
Diarrhoea (G3/4: 1.7%)

Constipation 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Skin reaction (G3/4: 0.8%)

Nail disorders (severe: 0.8%) 

Musculoskeletal and connective 
tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

Asthenia (severe: 12.4%);  
Fluid retention (severe: 0.8%); 
Pain 

 

Investigations  G3/4 Blood bilirubin increased 
(< 2%)

 



109 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with doxorubicin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 7.8%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
91.7%); 
Anaemia (G3/4: 9.4%); 
Febrile neutropenia; 
Thrombocytopenia (G4: 
0.8%) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
1.2%)

 

Metabolism and 
nutrition disorders 

 Anorexia  

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Cardiac disorders  Cardiac failure;  
Arrhythmia (no severe)

 

Vascular disorders  Hypotension 
Gastrointestinal 
disorders 

Nausea (G3/4: 5%);  
Stomatitis (G3/4: 
7.8%);  
Diarrhoea (G3/4: 6.2%); 
Vomiting (G3/4: 5%);  
Constipation 

  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.4%);  
Skin reaction (no 
severe) 

  

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  

General disorders and 
administration site 
conditions 

Asthenia (severe: 
8.1%);  
Fluid retention (severe: 
1.2%); 
Pain 

Infusion site reaction  

Investigations  G3/4 Blood bilirubin 
increased (< 2.5%); 
G3/4 Blood alkaline 
phosphatase increased 
(< 2.5%)

G3/4 AST increased 
(< 1%); 
G3/4 ALT increased 
(< 1%) 

 



110 

Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 5.7%)   

Blood and lymphatic 
system disorders 

Neutropenia (G4: 
51.5%);  
Anaemia (G3/4: 6.9%); 
Thrombocytopenia (G4: 
0.5%) 

Febrile neutropenia  

Immune system 
disorders 

Hypersensitivity (G3/4: 
2.5%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 3.7%); 
Peripheral motor 
neuropathy (G3/4: 2%)

  

Cardiac disorders  Arrhythmia (G3/4: 
0.7%)

Cardiac failure 

Vascular disorders  Hypotension (G3/4: 
0.7%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 9.6%);  
Vomiting (G3/4: 7.6%); 
Diarrhoea (G3/4: 6.4%); 
Stomatitis (G3/4: 2%)

Constipation  

Skin and subcutaneous 
tissue disorders 

Alopecia;  
Nail disorders (severe: 
0.7%);  
Skin reaction (G3/4: 
0.2%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 0.5%)   

General disorders and 
administration site 
conditions 

Asthenia (severe: 
9.9%); 
Fluid retention (severe: 
0.7%); 
Fever (G3/4: 1.2%)

Infusion site reaction;  
Pain 

 

Investigations  G3/4 Blood bilirubin 
increased (2.1%); 
G3/4 ALT increased 
(1.3%) 

G3/4 AST increased 
(0.5%);  
G3/4 Blood alkaline 
phosphatase increased 
(0.3%) 

 



111 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² in combination 
with trastuzumab 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Febrile neutropenia (includes 
neutropenia associated with 
fever and antibiotic use) or 
neutropenic sepsis 

 

Metabolism and nutrition 
disorders 

Anorexia  

Psychiatric disorders Insomnia
Nervous system disorders Paresthesia; Headache; 

Dysgeusia; Hypoaesthesia
 

Eye disorders Lacrimation increased; 
Conjunctivitis

 

Cardiac disorders  Cardiac failure 
Vascular disorders Lymphoedema
Respiratory, thoracic and 
mediastinal disorders 

Epistaxis; Pharyngolaryngeal 
pain; Nasopharyngitis; 
Dyspnoea;  
Cough; Rhinorrhoea

 

Gastrointestinal disorders Nausea; Diarrhoea; Vomiting; 
Constipation; Stomatitis; 
Dyspepsia; Abdominal pain

 

Skin and subcutaneous tissue 
disorders 

Alopecia; Erythema; Rash; Nail 
disorders

 

Musculoskeletal and connective 
tissue disorders 

Myalgia; Arthralgia; Pain in 
extremity; Bone pain; Back pain

 

General disorders and 
administration site conditions 

Asthenia; Oedema peripheral; 
Pyrexia; Fatigue; Mucosal 
inflammation; Pain; Influenza 
like illness; Chest pain; Chills

Lethargy 

Investigations Weight increased
 
Description of selected adverse reactions in breast cancer for Docetaxel Zentiva 100 mg/m² in 
combination with trastuzumab 
 
Blood and lymphatic system disorders 
Very common: Haematological toxicity was increased in patients receiving trastuzumab and 
docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 
criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 
known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 
incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 
Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 
 
Cardiac disorders 
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 
trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 
64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 
alone. 
 



112 

Tabulated list of adverse reactions in breast cancer for Docetaxel Zentiva 75 mg/m² in combination 
with capecitabine 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations  Oral candidiasis (G3/4: < 1%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 63%); 
Anaemia (G3/4: 10%)

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

Anorexia (G3/4: 1%);  
Decreased appetite 

Dehydration (G3/4: 2%) 

Nervous system disorders Dysgeusia (G3/4: < 1%); 
Paraesthesia (G3/4: < 1%) 

Dizziness;  
Headache (G3/4: < 1%);  
Neuropathy peripheral 

Eye disorders Lacrimation increased
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain (G3/4: 
2%) 

Dyspnoea (G3/4: 1%);  
Cough (G3/4: < 1%);  
Epistaxis (G3/4: < 1%) 

Gastrointestinal disorders Stomatitis (G3/4: 18%);  
Diarrhoea (G3/4: 14%);  
Nausea (G3/4: 6%);  
Vomiting (G3/4: 4%);  
Constipation (G3/4: 1%);  
Abdominal pain (G3/4: 2%);  
Dyspepsia

Abdominal pain upper;  
Dry mouth 

Skin and subcutaneous tissue 
disorders 

Hand-foot syndrome (G3/4: 
24%); 
Alopecia (G3/4: 6%);  
Nail disorders (G3/4: 2%) 

Dermatitis;  
Rash erythematous (G3/4: 
< 1%);  
Nail discolouration;  
Onycholysis (G3/4: 1%) 

Musculoskeletal and connective 
tissue disorders 

Myalgia (G3/4: 2%);  
Arthralgia (G3/4: 1%)

Pain in extremity (G3/4: < 1%); 
Back pain (G3/4: 1%) 

General disorders and 
administration site conditions 

Asthenia (G3/4: 3%);  
Pyrexia (G3/4: 1%);  
Fatigue/weakness (G3/4: 5%);  
Oedema peripheral (G3/4: 1%)

Lethargy; 
Pain 

Investigations  Weight decreased; 
G3/4 Blood bilirubin increased 
(9%)

 



113 

Tabulated list of adverse reactions in metastatic castration-resistant prostate cancer for Docetaxel 
Zentiva 75 mg/m² in combination with prednisone or prednisolone 
 
MedDRA system organ classes 
 

Very common adverse 
reactions 
 

Common adverse reactions 
 

Infections and infestations Infection (G3/4: 3.3%)
Blood and lymphatic system 
disorders 

Neutropenia (G3/4: 32%);  
Anaemia (G3/4: 4.9%) 

Thrombocytopenia (G3/4: 
0.6%); 
Febrile neutropenia 

Immune system disorders  Hypersensitivity (G3/4: 0.6%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 0.6%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 1.2%); 
Dysgeusia (G3/4: 0%)

Peripheral motor neuropathy 
(G3/4: 0%) 

Eye disorders  Lacrimation increased (G3/4: 
0.6%)

Cardiac disorders  Cardiac left ventricular function 
decrease (G3/4: 0.3%) 

Respiratory, thoracic and 
mediastinal disorders 

 Epistaxis (G3/4: 0%); 
Dyspnoea (G3/4: 0.6%);  
Cough (G3/4: 0%) 

Gastrointestinal disorders Nausea (G3/4: 2.4%);  
Diarrhoea (G3/4: 1.2%);  
Stomatitis/Pharyngitis (G3/4: 
0.9%);  
Vomiting (G3/4: 1.2%)

 

Skin and subcutaneous tissue 
disorders 

Alopecia;  
Nail disorders (no severe)

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

 Arthralgia (G3/4: 0.3%);  
Myalgia (G3/4: 0.3%) 

General disorders and 
administration site conditions 

Fatigue (G3/4: 3.9%); 
Fluid retention (severe: 0.6%)

 

 
Tabulated list of adverse reactions in high-risk locally advanced or  metastatic hormone-sensitive 
prostate cancer for DOCETAXEL 75 mg/m² in combination with prednisone prednisolone and ADT 
(STAMPEDE study)  
 
MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Blood and lymphatic system 
disorders 

Neutropenia (G3-4: 12 %) 
Anaemia  
Febrile neutropenia (G3-4: 15%) 

 

Immune system disorders   Hypersensitivity (G3-4: 1%) 

Endocrine disorders  Diabetes (G3-4: 1%) 

Metabolism and nutrition 
disorders 

 Anorexia  

Psychiatric disorders Insomnia (G3: 1%)  



114 

MedDRA system organ 
classes 

Very common adverse 
reactions 

Common adverse reactions 

Nervous system disorders Peripheral sensory neuropathy 
(≥G3: 2%)a 
Headache 
 

Dizziness 

Eye disorders  Blurred vision 

Cardiac disorders  Hypotension (G3: 0%) 

Respiratory, thoracic and 
mediastinal disorders  

Dyspnea (G3: 1%) 
Coughing (G3: 0%) 
Upper respiratory tract infection 
(G3: 1%) 

Pharyngitis (G3: 0%) 
 
 

Gastrointestinal disorders  Diarrhea (G3: 3%) 
Stomatitis (G3: 0%) 
Constipation (G3: 0%) 
Nausea (G3: 1%) 
Dyspepsia 
Abdominal pain (G3: 0%) 
Flatulence

Vomiting (G3: 1%) 
 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3: 3%)a 
Nail changes (G3: 1%) 

Rash 

Musculoskeletal and 
connective tissue disorders 

Myalgia   

General disorders and 
administration site conditions 

Lethargy (G3-4: 2%) 
Flu-like symptoms (G3: 0%) 
Asthenia (G3: 0%) 
Fluid retention 

Fever (G3: 1%) 
Oral candidiasis  
Hypocalcaemia (G3: 0%) 
Hypophosphataemia (G3-4: 1%) 
Hypokalaemia (G3: 0%) 

 
 
a From the GETUG AFU15 study 



115 

Tabulated list of adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer - pooled data 
 
MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 2.4%); 
Neutropenic infection 
(G3/4: 2.6%) 
 

  

Blood and lymphatic 
system disorders 

Anaemia (G3/4: 3%);  
Neutropenia (G3/4: 
59.2%); 
Thrombocytopenia 
(G3/4: 1.6%);  
Febrile neutropenia 
(G3/4: NA) 

  

Immune system 
disorders 

 Hypersensitivity (G3/4: 
0.6%)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 1.5%)   

Nervous system 
disorders 

Dysgeusia (G3/4: 
0.6%); 
Peripheral sensory 
neuropathy (G3/4: 
<0.1%) 

Peripheral motor 
neuropathy (G3/4: 0%)  

Syncope (G3/4: 0%); 
Neurotoxicity (G3/4: 
0%);  
Somnolence (G3/4: 0%)

Eye disorders Conjunctivitis (G3/4: 
<0.1%) 

Lacrimation increased 
(G3/4: <0.1%)  

 

Cardiac disorders  Arrhythmia (G3/4: 
0.2%)  

 

Vascular disorders Hot flush (G3/4: 0.5%) Hypotension (G3/4: 
0%); 
Phlebitis (G3/4: 0%)

Lymphoedema (G3/4: 
0%) 

Respiratory, thoracic 
and mediastinal 
disorders 

 Cough (G3/4: 0%)  

Gastrointestinal 
disorders 

Nausea (G3/4: 5.0%); 
Stomatitis (G3/4: 
6.0%);  
Vomiting (G3/4: 4.2%); 
Diarrhoea (G3/4: 3.4%);
Constipation (G3/4: 
0.5%)  

Abdominal pain (G3/4: 
0.4%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (persisting: 
<3%);  
Skin disorder (G3/4: 
0.6%);  
Nail disorders (G3/4: 
0.4%) 

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (G3/4: 0.7%); 
Arthralgia (G3/4: 0.2%)

  



116 

MedDRA System 
Organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Reproductive system 
and breast disorders 

Amenorrhoea (G3/4: 
NA) 

  

General disorders and 
administration site 
conditions 

Asthenia (G3/4: 
10.0%); 
Pyrexia (G3/4: NA); 
Oedema peripheral 
(G3/4: 0.2%) 

  

Investigations  Weight increased (G3/4: 
0%); 
Weight decreased 
(G3/4: 0.2%)

 

 
Description of selected adverse reactions for adjuvant therapy with Docetaxel Zentiva 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer 
 
Nervous system disorders 
In study TAX316 peripheral sensory neuropathy started during the treatment period and persisted into 
the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 
of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 
observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. 
In GEICAM 9805 study peripheral sensory neuropathy that started during the treatment period 
persisted into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC 
arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral 
sensory neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient 
(0.2%) in FAC arm. 
 
Cardiac disorders 
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 
congestive heart failure during the follow-up period. At the end of the follow-up period (actual median 
follow-up time of 10 years and 5 months), no patients  had CHF in TAC arm and  1 patient in TAC 
arm died because of dilated cardiomyopathy, and CHF was observed to be ongoing in 1 patient (0.2%) 
in FAC arm. 
 
Skin and subcutaneous tissue disorders 
In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 
At the end of the follow-up period (actual median follow-up time of	8 years), alopecia was observed to 
be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-
up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 
FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 
42 patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up 
period (median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 
patients (0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.   
 
Reproductive system and breast disorders 
In TAX316 amenorrhoea that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 



117 

FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 
(median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). 
In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 
follow-up period was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients (1.0 %) 
in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 months), 
amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients (0.8%) in 
FAC arm. 
 
General disorders and administration site conditions 
In study TAX316 peripheral oedema that started during the treatment period and persisted into the 
follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 
23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 
years), peripheral oedema was ongoing in19 TAC patients (2.6%) and 4 FAC patients (0.5%).  
In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-
up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 
FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 
lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). 
In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 
FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 
asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
 
In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 
follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 
the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 
had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm. 
Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 
(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 
lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 
FAC arm.  
Asthenia that started during the treatment period and persisted into the follow-up period was observed 
to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 
follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 
patients (0.4%) in FAC arm. 
 
Acute leukaemia / Myelodysplastic syndrome. 
After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients 
(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 
syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%).  
After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532 (0.2%) 
patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed with 
myelodysplastic syndrome in either treatment groups. 
 
Neutropenic complications 
Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 
infection was decreased in patients who received primary G-CSF prophylaxis after it was made 
mandatory in the TAC arm – GEICAM STUDY.  
 
Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 
(GEICAM 9805) 
 
 Without primary 

G-CSF prophylaxis 
(n = 111) 

n (%) 

With primary  
G-CSF prophylaxis 

(n = 421)  
n (%) 



118 

Neutropenia (Grade 4)  104 (93.7) 135 (32.1) 
 

Febrile neutropenia  28 (25.2) 23 (5.5) 
 

Neutropenic infection  14 (12.6) 21 (5.0) 
 

Neutropenic infection 
(Grade 3-4)  

2 (1.8) 5 (1.2) 

 
Tabulated list of adverse reactions in gastric adenocarcinoma cancer for Docetaxel Zentiva 75 mg/m² 
in combination with cisplatin and 5-fluorouracil 
 
MedDRA system organ classes Very common adverse 

reactions 
 

Common adverse reactions 
 

Infections and infestations Neutropenic infection; 
Infection (G3/4: 11.7%)

 

Blood and lymphatic system 
disorders 

Anaemia (G3/4: 20.9%); 
Neutropenia (G3/4: 83.2%);  
Thrombocytopenia (G3/4: 
8.8%); 
Febrile neutropenia 

 

Immune system disorders Hypersensitivity (G3/4: 1.7%)
Metabolism and nutrition 
disorders 

Anorexia (G3/4: 11.7%)  

Nervous system disorders Peripheral sensory neuropathy 
(G3/4: 8.7%) 

Dizziness (G3/4: 2.3%);  
Peripheral motor neuropathy 
(G3/4: 1.3%) 

Eye disorders  Lacrimation increased (G3/4: 
0%)

Ear and labyrinth disorders  Hearing impaired (G3/4: 0%)
Cardiac disorders  Arrhythmia (G3/4: 1.0%) 
Gastrointestinal disorders Diarrhoea (G3/4: 19.7%);  

Nausea (G3/4: 16%);  
Stomatitis (G3/4: 23.7%); 
Vomiting (G3/4: 14.3%) 

Constipation (G3/4: 1.0%); 
Gastrointestinal pain (G3/4: 
1.0%); 
Oesophagitis/dysphagia/odynop
hagia (G3/4: 0.7%) 

Skin and subcutaneous tissue 
disorders 

Alopecia (G3/4: 4.0%) Rash pruritus (G3/4: 0.7%);  
Nail disorders (G3/4: 0.7%);  
Skin exfoliation (G3/4: 0%)

General disorders and 
administration site conditions 

Lethargy (G3/4: 19.0%); 
Fever (G3/4: 2.3%); 
Fluid retention 
(severe/life-threatening: 1%)

 

 
Description of selected adverse reactions in gastric adenocarcinoma cancer for Docetaxel 
Zentiva 75 mg/m2 in combination with cisplatin and 5-fluorouracil 
 
Blood and lymphatic system disorders 
Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 
regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 
the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 
patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 
prophylactic G-CSF (see section 4.2). 
Tabulated list of adverse reactions in head and neck cancer for Docetaxel Zentiva 75 mg/m² in 
combination with cisplatin and 5-fluorouracil 



119 

 
 Induction chemotherapy followed by radiotherapy (TAX 323) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 6.3%); 
Neutropenic infection

  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
0.6%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
76.3%); 
Anaemia (G3/4: 9.2%); 
Thrombocytopenia 
(G3/4: 5.2%) 

Febrile neutropenia  

Immune system 
disorders 

 Hypersensitivity (no 
severe)

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 0.6%)   

Nervous system 
disorders 

Dysgeusia/Parosmia; 
Peripheral sensory 
neuropathy (G3/4: 
0.6%) 

Dizziness  

Eye disorders  Lacrimation increased; 
Conjunctivitis 

 

Ear and labyrinth 
disorders 

 Hearing impaired  

Cardiac disorders  Myocardial ischemia 
(G3/4:1.7%)

Arrhythmia (G3/4: 
0.6%) 

Vascular disorders  Venous disorder (G3/4: 
0.6%)

 

Gastrointestinal 
disorders 

Nausea (G3/4: 0.6%); 
Stomatitis (G3/4: 
4.0%); 
Diarrhoea (G3/4: 2.9%);
Vomiting (G3/4: 0.6%) 

Constipation; 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
0.6%); 
Abdominal pain; 
Dyspepsia; 
Gastrointestinal 
haemorrhage (G3/4: 
0.6%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 10.9%) Rash pruritic; 
Dry skin;  
Skin exfoliative (G3/4: 
0.6%)

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.6%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 3.4%); 
Pyrexia (G3/4: 0.6%); 
Fluid retention; 
Oedema 

  

Investigations  Weight increased
 



120 

 Induction chemotherapy followed by chemoradiotherapy (TAX 324) 
 
MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 3.6%) 
 

Neutropenic infection  

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

 Cancer pain (G3/4: 
1.2%) 

 

Blood and lymphatic 
system disorders 

Neutropenia (G3/4: 
83.5%); 
Anaemia (G3/4: 
12.4%); 
Thrombocytopenia 
(G3/4: 4.0%); 
Febrile neutropenia

  

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 
12.0%) 

  

Nervous system 
disorders 

Dysgeusia/Parosmia 
(G3/4: 0.4%); 
Peripheral sensory 
neuropathy (G3/4: 
1.2%) 

Dizziness (G3/4: 
2.0%); 
Peripheral motor 
neuropathy (G3/4: 
0.4%)

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia (G3/4: 
2.0%)

Ischemia myocardial 

Vascular disorders  Venous disorder
Gastrointestinal 
disorders 

Nausea (G3/4: 13.9%); 
Stomatitis (G3/4: 
20.7%); 
Vomiting (G3/4: 
8.4%); 
Diarrhoea (G3/4: 
6.8%); 
Esophagitis/dysphagia/ 
odynophagia (G3/4: 
12.0%); 
Constipation (G3/4: 
0.4%) 

Dyspepsia (G3/4: 
0.8%); 
Gastrointestinal pain 
(G3/4: 1.2%); 
Gastrointestinal 
haemorrhage (G3/4: 
0.4%) 
 

 

Skin and subcutaneous 
tissue disorders 

Alopecia (G3/4: 4.0%); 
Rash pruritic 

Dry skin ; 
Desquamation

 

Musculoskeletal, 
connective tissue bone 
disorders 

 Myalgia (G3/4: 0.4%)  

General disorders and 
administration site 
conditions 

Lethargy (G3/4: 4.0%); 
Pyrexia (G3/4: 3.6%); 
Fluid retention (G3/4: 
1.2%); 
Oedema (G3/4: 1.2%)

  

Investigations Weight decreased Weight increased



121 

 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 
Second primary malignancies (frequency not known), including non-Hodgkin lymphoma have been 
reported in association with docetaxel when used in combination with other anticancer treatments 
known to be associated with second primary malignancies. Acute myeloid leukaemia and 
myelodysplastic syndrome have been reported (frequency uncommon) in pivotal clinical studies in 
breast cancer with TAC regimen. 
 
Blood and lymphatic system disorders 
Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been 
reported. 
 
Immune system disorders 
Some cases of anaphylactic shock, sometimes fatal, have been reported.  
Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 
previously experienced hypersensitivity reactions to paclitaxel. 
 
Nervous system disorders 
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 
administration. These reactions sometimes appear during the infusion of the medicinal product. 
 
Eye disorders 
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 
during infusion of the medicinal product and in association with hypersensitivity reactions have been 
reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 
without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 
rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 
docetaxel. 
 
Ear and labyrinth disorders 
Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 
 
Cardiac disorders 
Rare cases of myocardial infarction have been reported. 
Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 
been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-
fluorouracil and/ or cyclophosphamide. 
 
Vascular disorders 
Venous thromboembolic events have rarely been reported. 
 
Respiratory, thoracic and mediastinal disorders 
Acute respiratory distress syndrome and cases of interstitial pneumonia/ pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.  
 
Gastrointestinal disorders 
Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 
reported with a potential fatal outcome (frequency not known). 
Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events 
including enterocolitis and gastrointestinal perforation.  
Rare cases of ileus and intestinal obstruction have been reported. 
 
Hepatobiliary disorders 



122 

Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 
 
Skin and subcutaneous tissue disorders  
Cases of cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe 
cutaneous adverse reactions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis 
(TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with docetaxel. 
Sclerodermal-like changes usually preceded by peripheral lymphoedema have been reported with 
docetaxel. Cases of permanent alopecia (frequency not known) have been reported. 
 
Renal and urinary disorders 
Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 
risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and gastro-
intestinal disorders. 
 
General disorders and administration site conditions 
Radiation recall phenomena have rarely been reported.  
Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 
administration of docetaxel at a different site) has been observed at the site of previous extravasation 
(frequency not known). 
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 
 
Metabolism and nutrition disorders 
Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 
mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 
hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 
with diarrhoea. 
 
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 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Taxanes, ATC Code: L01CD02 
 
Mechanism of action 
 
Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 
microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 
binding of docetaxel to microtubules does not alter the number of protofilaments. 
 



123 

Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 
vital mitotic and interphase cellular functions.  
 
Pharmacodynamic effects 
 
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 
against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 
concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 
but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 
gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour 
activity against advanced murine and human grafted tumours. 
 
Clinical efficacy and safety 
 
Breast cancer 
 
Docetaxel Zentiva in combination with doxorubicin and cyclophosphamide: adjuvant therapy 
 
Patients with operable node-positive breast cancer (TAX 316) 
 
Data from a multi-centre open label randomised study support the use of docetaxel for the adjuvant 
treatment of patients with operable node-positive breast cancer and KPS  80%, between 18 and 
70 years of age. After stratification according to the number of positive lymph nodes (1-3, 4+), 
1491 patients were randomised to receive either docetaxel 75 mg/m2 administered 1-hour after 
doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 
followed by fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 (FAC arm). Both regimens 
were administered once every 3 weeks for 6 cycles. Docetaxel was administered as a 1-hour infusion, 
all other medicinal products were given as intravenous bolus on day one. G-CSF was administered as 
secondary prophylaxis to patients who experienced complicated neutropenia (febrile neutropenia, 
prolonged neutropenia, or infection). Patients on the TAC arm received antibiotic prophylaxis with 
ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. In 
both arms, after the last cycle of chemotherapy, patients with positive oestrogen and/or progesterone 
receptors received tamoxifen 20 mg daily for up to 5 years. Adjuvant radiation therapy was prescribed 
according to guidelines in place at participating institutions and was given to 69% of patients who 
received TAC and 72% of patients who received FAC.  
Two interim analyses and one final analysis were performed. The first interim analysis was planned 3 
years after the date when half of study enrolment was done. The second interim analysis was done 
after 400 DFS events had been recorded overall, which led to a median follow-up of 55 months. The 
final analysis was performed when all patients had reached their 10-year follow-up visit (unless they 
had a DFS event or were lost to follow-up before). Disease-free survival (DFS) was the primary 
efficacy endpoint and overall survival (OS) was the secondary efficacy endpoint. 
 
A final analysis was performed with an actual median follow-up of 96 months. Significantly longer 
disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 
relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 
(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). Overall survival at 
10 years was also significantly increased with TAC compared to FAC (76% versus 69%, respectively) 
i.e. an absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients 
with 4+ nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC 
in patients with 4+ nodes was not fully demonstrated at the final analysis. 
  
 
Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analysed: 
 



124 

  Disease free survival Overall survival 
Patient subset Number 

of 
patients 

Hazard 
ratio* 

95% CI p = Hazard 
ratio* 

95% CI p = 

No of positive 
nodes 

       

Overall 745 0.80 0.68-0.93 0.0043 0.74 0.61-0.90 0.0020
1-3 467 0.72 0.58-0.91 0.0047 0.62 0.46-0.82 0.0008
4+ 278 0.87 0.70-1.09 0.2290 0.87 0.67-1.12 0.2746
*a hazard ratio of less than 1 indicates that TAC is associated with a longer disease-free survival and 
overall survival compared to FAC 
 
Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805)  
 
Data from a multicenter open label randomised trial support the use of Docetaxel Zentiva for the 
adjuvant treatment of patients with operable node-negative breast cancer eligible to receive 
chemotherapy . 1060 patients were randomised to receive either Docetaxel Zentiva 75 mg/m2 
administered 1-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (539 patients in 
TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclophosphamide 
500 mg/m2 (521 patients in FAC arm), as adjuvant treatment of operable node-negative breast cancer 
patients with high risk of relapse according to 1998 St. Gallen criteria (tumour size >2 cm and/or 
negative ER and PR and/or high histological/nuclear grade (grade 2 to 3) and /or age <35 years).). 
Both regimens were administered once every 3 weeks for 6 cycles. Docetaxel Zentiva was 
administered as a 1-hour infusion, all other medicinal products were given intravenously on day 1 
every three weeks. Primary prophylactic G-CSF was made mandatory in TAC arm after 230 patients 
were randomised. The incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infection 
was decreased in patients who received primary G-CSF prophylaxis (see section 4.8). In both arms, 
after the last cycle of chemotherapy, patients with ER+ and/or PgR+ tumours received tamoxifen 
20 mg once a day for up to 5 years. Adjuvant radiation therapy was administered according to 
guidelines in place at participating institutions and was given to 57.3% of patients who received TAC 
and 51.2% of patients who received FAC. 
 
One primary analysis and one updated analysis were performed. The primary analysis was done when 
all patients had a follow-up of greater than 5 years (median follow-up time of 77 months). The updated 
analysis was performed when all patients had reached their 10-year (median follow up time of 10 
years and 5 months) follow-up visit (unless they had a DFS event or were lost to follow-up 
previously). Disease-free survival (DFS) was the primary efficacy endpoint and Overall survival (OS) 
was the secondary efficacy endpoint. 
 
At the median follow-up time of 77 months, significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01). At the 
median follow up time of 10 years and 5 months, TAC-treated patients had a 16,5% reduction in the 
risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 
p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 
favour of TAC.   
 
At the median follow-up time of 77 months, overall survival (OS) was longer in the TAC arm with 
TAC-treated patients having a 24% reduction in the risk of death compared to FAC (hazard 
ratio = 0.76, 95% CI (0.46-1.26, p = 0.29). However, the distribution of OS was not significantly 
different between the 2 groups. 
At the median follow up time of 10 years and 5 months, TAC-treated patients had a 9% reduction in 
the risk of death compared to FAC-treated patients (hazard ratio = 0.91, 95% CI (0.63-1.32)).  
The survival rate was 93.7% in the TAC arm and 91.4 % in the FAC arm, at the 8-year follow-up time 
point, and 91.3 % in the TAC arm and 89 % in the FAC arm, at the 10-year follow-up time point. 
 



125 

The positive benefit risk ratio for TAC compared to FAC remained unchanged.   
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were analysed 
in the primary analysis (at the median follow-up time of 77 months) (see table below): 



126 

 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study  
(Intent-to-Treat Analysis) 

 
  Disease Free Survival 
Patient subset Number of patients 

in TAC group 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1   
<50 years 260 0.67 0.43-1.05 
≥50 years 279 0.67 0.43-1.05 
Age category 2   
<35 years 42 0.31 0.11-0.89 
≥35 years 497 0.73 0.52-1.01 
Hormonal receptor 
status 

   

Negative 195 0.7 0.45-1.1 
Positive 344 0.62 0.4-0.97 
Tumour size    
2 cm 285 0.69 0.43-1.1 
>2 cm 254 0.68 0.45-1.04 
Histological grade   
Grade1 (includes grade 
not assessed) 

64 0.79 0.24-2.6 

Grade 2 216 0.77 0.46-1.3 
Grade 3 259 0.59 0.39-0.9 
Menopausal status   
Pre-Menopausal 285 0.64 0.40-1 
Post-Menopausal 254 0.72 0.47-1.12 
*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free survival 
compared to FAC. 
 
Exploratory subgroup analyses for  disease-free survival for  patients who meet the 2009 St. Gallen 
chemotherapy criteria – (ITT population) were performed and presented here below: 
 
  

TAC 
 

FAC 
Hazard ratio 
(TAC/FAC) 

 
 

Subgroups (n=539) (n=521) (95% CI) p-value
 
Meeting relative indication 
for chemotherapy a 

    

 
No 

 
18/214 
(8.4%)

 
26/227 
(11.5%)

 
0.796 (0.434 - 1.459) 

 
0.4593 

 
Yes 

 
48/325 
(14.8%)

 
69/294 
(23.5%)

 
0.606 (0.42 - 0.877) 

 
0.0072 

TAC = docetaxel, doxorubicin and cyclophosphamide 
FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 
CI = confidence interval 
ER = oestrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 



127 

Docetaxel Zentiva as single agent 
 
Two randomised phase III comparative studies, involving a total of 326 alkylating or 
392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 
recommended dose and regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p = 0.38) or 
time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p = 0.54), docetaxel increased 
response rate (52% vs. 37%, p = 0.01) and shortened time to response (12 weeks vs. 23 weeks, 
p = 0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 
15 doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 
failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 
(33% vs. 12%, p < 0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p = 0.0004) and 
prolonged overall survival (11 months vs. 9 months, p = 0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety profile 
observed in phase II studies (see section 4.8).  
 
An open-label, multi-centre, randomised phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 
therapy should have included an anthracycline. A total of 449 patients were randomised to receive 
either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 
infusion. Both regimens were administered every 3 weeks. 
Without affecting the primary endpoint, overall response rate (32% vs 25%, p = 0.10), docetaxel 
prolonged median time to progression (24.6 weeks vs 15.6 weeks; p < 0.01) and median survival 
(15.3 months vs 12.7 months; p = 0.03). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%).  
 
Docetaxel Zentiva in combination with doxorubicin 
 
One large randomised phase III study, involving 429 previously untreated patients with metastatic 
disease, has been performed with doxorubicin (50 mg/m²) in combination with docetaxel (75 mg/m²) 
(AT arm) versus doxorubicin (60 mg/m²) in combination with cyclophosphamide (600 mg/m²) 
(AC arm). Both regimens were administered on day 1 every 3 weeks. 
 
 Time to progression (TTP) was significantly longer in the AT arm versus AC arm, p = 0.0138. 
The median TTP was 37.3 weeks (95% CI: 33.4 - 42.1) in AT arm and 31.9 weeks (95% CI: 
27.4 - 36.0) in AC arm. 
 Overall response rate (ORR) was significantly higher in the AT arm versus AC arm, p = 0.009. 
The ORR was 59.3% (95% CI: 52.8 - 65.9) in AT arm versus 46.5% (95% CI: 39.8 - 53.2) in AC arm. 
 
In this study, AT arm showed a higher incidence of severe neutropenia (90% versus 68.6%), febrile 
neutropenia (33.3% versus 10%), infection (8% versus 2.4%), diarrhoea (7.5% versus 1.4%), asthenia 
(8.5% versus 2.4%), and pain (2.8% versus 0%) than AC arm. On the other hand, AC arm showed a 
higher incidence of severe anaemia (15.8% versus 8.5%) than AT arm, and, in addition, a higher 
incidence of severe cardiac toxicity: congestive heart failure (3.8% versus 2.8%), absolute LVEF 
decrease  20% (13.1% versus 6.1%), absolute LVEF decrease  30% (6.2% versus 1.1%). Toxic 
deaths occurred in 1 patient in the AT arm (congestive heart failure) and in 4 patients in the AC arm 
(1 due to septic shock and 3 due to congestive heart failure). 
In both arms, quality of life measured by the EORTC questionnaire was comparable and stable during 
treatment and follow-up. 
 



128 

Docetaxel Zentiva in combination with trastuzumab 
 
Docetaxel in combination with trastuzumab was studied for the treatment of patients with metastatic 
breast cancer whose tumours overexpress HER2, and who previously had not received chemotherapy 
for metastatic disease. One hundred eighty six patients were randomised to receive docetaxel 
(100 mg/m2) with or without trastuzumab; 60% of patients received prior anthracycline-based adjuvant 
chemotherapy. Docetaxel plus trastuzumab was efficacious in patients whether or not they had 
received prior adjuvant anthracyclines. The main test method used to determine HER2 positivity in 
this pivotal study was immunohistochemistry (IHC). A minority of patients were tested using 
fluorescence in-situ hybridization (FISH). In this study, 87% of patients had disease that was IHC 3+, 
and 95% of patients entered had disease that was IHC 3+ and/or FISH positive. Efficacy results are 
summarized in the following table: 
 

Parameter Docetaxel plus trastuzumab1 
n = 92

Docetaxel1 
n = 94 

Response rate  
(95% CI) 

61% 
(50-71)

34% 
(25-45) 

Median duration of response 
(months) 
(95% CI) 

 
11.4 

(9.2-15.0)

 
5.1 

(4.4-6.2) 
Median TTP (months) 
(95% CI) 

10.6 
(7.6-12.9)

5.7 
(5.0-6.5) 

Median survival (months) 
(95% CI) 

30.52 
(26.8-ne)

22.12 
(17.6-28.9) 

TTP = time to progression; “ne” indicates that it could not be estimated or it was not yet reached. 
1Full analysis set (intent-to-treat) 
2 Estimated median survival 

 
Docetaxel Zentiva in combination with capecitabine 
 
Data from one multi-centre, randomised, controlled phase III clinical study support the use of 
docetaxel in combination with capecitabine for treatment of patients with locally advanced or 
metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline. In this 
study, 255 patients were randomised to treatment with docetaxel (75 mg/m2 as a 1 hour intravenous 
infusion every 3 weeks) and capecitabine (1250 mg/m2 twice daily for 2 weeks followed by 1-week 
rest period). 256 patients were randomised to treatment with docetaxel alone (100 mg/m2 as a 1 hour 
intravenous infusion every 3 weeks). Survival was superior in the docetaxel + capecitabine 
combination arm (p = 0.0126). Median survival was 442 days (docetaxel + capecitabine) vs. 352 days 
(docetaxel alone). The overall objective response rates in the all-randomised population (investigator 
assessment) were 41.6% (docetaxel + capecitabine) vs. 29.7% (docetaxel alone); p = 0.0058. Time to 
progressive disease was superior in the docetaxel + capecitabine combination arm (p < 0.0001). The 
median time to progression was 186 days (docetaxel + capecitabine) vs. 128 days (docetaxel alone). 
 
Non-small cell lung cancer 
 
Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 
and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 
Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 
There was less use of morphinic analgesic (p < 0.01), non-morphinic analgesics (p < 0.01), other 
disease-related medicinal products (p = 0.06) and radiotherapy (p < 0.01) in patients treated with 
docetaxel at 75 mg/m² compared to those with BSC. 
The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 
26.1 weeks. 
 



129 

Docetaxel Zentiva in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 
administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 
day 1 of cycles repeated every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated 
in the following table: 
 

 TCis 
n = 408

VCis 
n = 404

Statistical analysis 

Overall survival  
(Primary end-point):

   

Median survival (months) 11.3 10.1 Hazard Ratio: 1.122 
[97.2% CI: 0.937; 1.342]*

1-year Survival (%) 46 41 Treatment difference: 5.4% 
[95% CI: -1.1; 12.0] 

2-year Survival (%) 21 14 Treatment difference: 6.2% 
[95% CI: 0.2; 12.3] 

Median time to progression 
(weeks): 

 
22.0 

 
23.0 

 
Hazard Ratio: 1.032 

[95% CI: 0.876; 1.216] 
Overall response rate (%): 31.6 24.5 Treatment difference: 7.1% 

[95% CI: 0.7; 13.5] 
*: Corrected for multiple comparisons and adjusted for stratification factors (stage of disease and 
region of treatment), based on evaluable patient population. 

 
Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnofsky performance status. Results on these end-points 
were supportive of the primary end-points results.  
 
For docetaxel/carboplatin combination, neither equivalent nor non-inferior efficacy could be proven 
compared to the reference treatment combination VCis. 
 
Prostate cancer 
 
Metastatic castration-resistant prostate cancer 
 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
metastatic castration-resistant prostate cancer were evaluated in a randomised multi-centre phase III 
study (TAX 327). A total of 1006 patients with KPS  60 were randomised to the following treatment 
groups: 
 Docetaxel 75 mg/m2 every 3 weeks for 10 cycles. 
 Docetaxel 30 mg/m2 administered weekly for the first 5 weeks in a 6 week cycle for 5 cycles. 
 Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles. 
All 3 regimens were administered in combination with prednisone or prednisolone 5 mg twice daily, 
continuously. 
 
Patients who received docetaxel every three weeks demonstrated significantly longer overall survival 
compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 
arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 
the docetaxel arms versus the control arm are summarized in the following table: 



130 

 
Endpoint 
 

Docetaxel  
every 3 weeks 

Docetaxel  
every week

Mitoxantrone  
every 3 weeks 

Number of patients 
Median survival (months) 
95% CI 
Hazard ratio 
95% CI 
p-value†* 

335 
18.9 

(17.0-21.2) 
0.761 

(0.619-0.936) 
0.0094

334 
17.4 

(15.7-19.0) 
0.912 

(0.747-1.113) 
0.3624

337 
16.5 

(14.4-18.6) 
-- 
-- 
-- 

Number of patients 
PSA** response rate (%) 
95% CI 
p-value* 

291 
45.4 

(39.5-51.3) 
0.0005

282 
47.9 

(41.9-53.9) 
<0.0001

300 
31.7 

(26.4-37.3) 
-- 

Number of patients 
Pain response rate (%) 
95% CI 
p-value* 

153 
34.6 

(27.1-42.7) 
0.0107

154 
31.2 

(24.0-39.1) 
0.0798

157 
21.7 

(15.5-28.9) 
-- 

Number of patients 
Tumour response rate (%) 
95% CI 
p-value* 

141 
12.1 

(7.2-18.6) 
0.1112 

134 
8.2 

(4.2-14.2) 
0.5853 

137 
6.6 

(3.0-12.1) 
-- 

†Stratified log rank test 
*Threshold for statistical significance = 0.0175 
**PSA: Prostate-Specific Antigen 
 
Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 
3 weeks, it is possible that certain patients may benefit from docetaxel every week. 
 
No statistical differences were observed between treatment groups for Global Quality of Life. 
 
Metastatic hormone-sensitive prostate cancer 
STAMPEDE study 
 
The safety and efficacy of docetaxel administered concomitantly with standard of care (ADT) in 
patients with high-risk locally advanced or metastatic hormone-sensitive prostate cancer were 
evaluated in a randomised multi-centre, multi-arm multi-stage (MAMS) study with a seamless phase 
II/III design (STAMPEDE – MRC PR08). A total of 1776 male patients were allocated to the 
treatment arms of interest:  
 Standard of care + docetaxel 75 mg/m², administered every 3 weeks for 6 cycles    
 Standard of care alone  
Docetaxel regimen was administered in combination with prednisone or prednisolone 5 mg twice daily 
continuously.  
Among the 1776 randomised patients 1086 (61%) had metastatic disease, 362 were randomised to 
docetaxel in combination with standard of care, 724 received standard of care alone.  
 
In these metastatic prostate cancer patients, the median overall survival was significantly longer in 
docetaxel treatment groups than in the standard of care alone group, with a median overall survival 19 
months longer with the addition of docetaxel to standard of care (HR =  0.76, 95% CI = 0.62-0.92, 
p=0.005).  
 
Efficacy results in metastatic prostate cancer patients for docetaxel arm versus control arm are 
summarized in the following table: 
 
 



131 

Efficacy of docetaxel in combination with prednisone or prednisolone and standard of care in the 
treatment of patients with metastatic hormone-sensitive prostate cancer (STAMPEDE) 
 

Endpoint 
 

Docetaxel + standard of care 
 

Standard of care alone 

Number of metastatic prostate 
cancer patients 
 
Median overall survival (months)  
95% CI 

362 
 
 

62 
51-73 

724 
 
 

43 
40-48 

Adjusted hazard ratio 
95% CI 
p-valuea 

0.76 
(0.62-0.92) 

0.005 

Failure-Free survivalb    
Median (months) 
95% CI 

20.4 
16.8-25.2

12 
9.6-12 

Adjusted hazard ratio 
95% CI 
p-valuea 

0.66 
(0.57-0.76) 

< 0.001 
a p-value calculated from the likelihood ratio test and adjusted for all stratification factors 
(except center and planned hormone therapy) and stratified by trial period 
b Failure-free survival: time from randomization to first evidence of at least one of: biochemical 
failure (defined as a rise in PSA of 50% above the within-24-week nadir and above 4 ng/mL 
and confirmed by retest or treatment); progression either locally, in lymph nodes, or in distant 
metastases; skeletal-related event; or death from prostate cancer. 
 

 
 
CHAARTED study 
 
The safety and efficacy of docetaxel administered at the beginning of androgen-deprivation therapy 
(ADT) in patients with metastatic hormone-sensitive prostate cancer were evaluated in a randomised 
Phase III multi-centre study (CHAARTED). A total of 790 male patients were allocated to the 2 
treatment groups.  

 ADT + docetaxel 75 mg/m² given at the beginning of ADT, administered every 3 weeks 
for 6 cycles 

 ADT alone   
 
The median overall survival was significantly longer in docetaxel treatment group than in the ADT 
alone group, with a median overall survival 13.6 months  longer with the addition of docetaxel to ADT 
(hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.47-0.80, p=0.0003).  
 
Efficacy results or the docetaxel arm versus the control arm are summarized in the following table: 
 



132 

Efficacy of docetaxel and ADT in the treatment of patients with metastatic hormone-sensitive prostate 
cancer (CHAARTED) 
 

Endpoint 
 

Docetaxel +ADT  
 

ADT alone 

Number of patients 
Median overall survival (months) 
All patients 
95% CI 
Adjusted hazard ratio 

397 
 

57.6 
49.1-72.8 

0.61 

393 
 

44.0 
34.4-49.1 

-- 
95% CI (0.47-0.80)  --
p-valuea 0.0003 -- 
Progression Free Survival 
Median (months) 
95% CI 
Adjusted hazard ratio 
95% CI 
p-value* 

 
19.8 

16.7-22.8 
0.60 

0.51-0.72 
P<0.0001 

 
11.6 

10.8-14.3 
-- 
-- 
-- 

PSA response** at 6 months – N(%) 
p-valuea* 

127 (32.0) 
<0.0001 

77 (19.6) 
-- 

PSA response** at 12 months – N(%) 
p-valuea* 

110 (27.7) 
<0.0001 

66 (16.8) 
-- 

Time to castration-resistant prostate cancerb   
Median (months)  
95% CI 
Adjusted hazard ratio 

20.2 
(17.2-23.6) 

0.61 

11.7 
(10.8-14.7) 

-- 
95% CI (0.51-0.72) --
p-valuea* <0.0001 -- 

Time to clinical progressionc    
Median (months)  33.0 19.8
95% CI (27.3-41.2) (17.9-22.8)
Adjusted hazard ratio 0.61 -- 
95% CI (0.50-0.75) --
p-valuea* <0.0001 -- 
a Time to event variables: Stratified log-rank test.  
  Response rate variables: Fisher's Exact test  
* p-value for descriptive purpose. 
** PSA response: Prostate-Specific Antigen response: PSA level <0.2 ng/mL measured for two 
consecutive measurements at least 4 weeks apart. 
b Time to castration-resistant prostate cancer = time from randomization to PSA progression or 
clinical progression (i.e., increasing symptomatic bone metastases, progression per Response 
Evaluation Criteria in Solid Tumours (RECIST) criteria, or clinical deterioration due to cancer 
per the Investigator’s opinion), whichever occurred first. 
c The time to clinical progression = the time from randomization until clinical progression (i.e., 
increased symptoms of bone metastases; progression according to RECIST; or clinical deterioration 
due to cancer according to the investigator’s opinion).
 
 
Gastric adenocarcinoma 
 
A multi-centre, open-label, randomised study was conducted to evaluate the safety and efficacy of 
docetaxel for the treatment of patients with metastatic gastric adenocarcinoma, including 
adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for 



133 

metastatic disease. A total of 445 patients with KPS > 70 were treated with either docetaxel (T) 
(75 mg/m2 on day 1) in combination with cisplatin (C) (75 mg/m2 on day 1) and 5-fluorouracil (F) 
(750 mg/m2 per day for 5 days) or cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per 
day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF 
arm. The median number of cycles administered per patient was 6 (with a range of 1-16) for the TCF 
arm compared to 4 (with a range of 1-12) for the CF arm. Time to progression (TTP) was the primary 
endpoint. The risk reduction of progression was 32.1% and was associated with a significantly longer 
TTP (p = 0.0004) in favour of the TCF arm. Overall survival was also significantly longer 
(p = 0.0201) in favour of the TCF arm with a risk reduction of mortality of 22.7%. Efficacy results are 
summarized in the following table: 
 
Efficacy of docetaxel in the treatment of patients with gastric adenocarcinoma 

 
Endpoint TCF 

n = 221
CF 

n = 224
Median TTP (months) 5.6 3.7 
(95% CI) (4.86-5.91) (3.45-4.47) 
Hazard ratio 1.473 
(95% CI) (1.189-1.825) 
*p-value 0.0004 
Median survival (months) 9.2 8.6 
(95% CI) (8.38-10.58) (7.16-9.46)
2-year estimate (%) 18.4 8.8 
Hazard ratio 1.293 
(95% CI) (1.041-1.606) 
*p-value 0.0201 
Overall response rate (CR+PR) (%) 36.7 25.4 
p-value 0.0106 
Progressive disease as best overall response (%) 16.7 25.9 

*Unstratified log rank test 
 
Subgroup analyses across age, gender and race consistently favoured the TCF arm compared to the CF 
arm. 
 
A survival update analysis conducted with a median follow-up time of 41.6 months no longer showed 
a statistically significant difference although always in favour of the TCF regimen and showed that the 
benefit of TCF over CF is clearly observed between 18 and 30 months of follow up. 
 
Overall, quality of life (QoL) and clinical benefit results consistently indicated improvement in favour 
of the TCF arm. Patients treated with TCF had a longer time to 5% definitive deterioration of global 
health status on the QLQ-C30 questionnaire (p = 0.0121) and a longer time to definitive worsening of 
Karnofsky performance status (p = 0.0088) compared to patients treated with CF. 
 
Head and neck cancer 
 
 Induction chemotherapy followed by radiotherapy (TAX323) 
The safety and efficacy of docetaxel in the induction treatment of patients with squamous cell 
carcinoma of the head and neck (SCCHN) was evaluated in a phase III, multi-centre, open-label, 
randomised study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO perfomance status 0 or 1, were randomised to one of two treatment arms. Patients on the 
docetaxel arm received docetaxel (T) 75 mg/m2 followed by cisplatin (P) 75 mg/m2 followed by 
5-fluorouracil (F) 750 mg/m2 per day as a continuous infusion for 5 days. This regimen was 
administered every three weeks for 4 cycles in case at least a minor response (≥ 25% reduction in 
bidimensionally measured tumour size) was observed after 2 cycles. At the end of chemotherapy, with 
a minimal interval of 4 weeks and a maximal interval of 7 weeks, patients whose disease did not 
progress received radiotherapy (RT) according to institutional guidelines for 7 weeks (TPF/RT). 
Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 



134 

1000 mg/m2 per day for 5 days. This regimen was administered every three weeks for 4 cycles in case 
at least a minor response (≥ 25% reduction in bidimensionally measured tumour size) was observed 
after 2 cycles. At the end of chemotherapy, with a minimal interval of 4 weeks and a maximal interval 
of 7 weeks, patients whose disease did not progress received radiotherapy (RT) according to 
institutional guidelines for 7 weeks (PF/RT). Locoregional therapy with radiation was delivered either 
with a conventional fraction (1.8 Gy - 2.0 Gy once a day, 5 days per week for a total dose of 66 to 
70 Gy), or accelerated/hyperfractionated regimens of radiation therapy (twice a day, with a minimum 
interfraction interval of 6 hours, 5 days per week). A total of 70 Gy was recommended for accelerated 
regimens and 74 Gy for hyperfractionated schemes. Surgical resection was allowed following 
chemotherapy, before or after radiotherapy. Patients on the TPF arm received antibiotic prophylaxis 
with ciprofloxacin 500 mg orally twice daily for 10 days starting on day 5 of each cycle, or equivalent. 
The primary endpoint in this study, progression-free survival (PFS), was significantly longer in the 
TPF arm compared to the PF arm, p = 0.0042 (median PFS: 11.4 vs. 8.3 months respectively) with an 
overall median follow up time of 33.7 months. Median overall survival was also significantly longer in 
favour of the TPF arm compared to the PF arm (median OS: 18.6 vs. 14.5 months respectively) with a 
28% risk reduction of mortality, p = 0.0128. Efficacy results are presented in the table below: 
 
Efficacy of docetaxel in the induction treatment of patients with inoperable locally advanced SCCHN 
(Intent-to-Treat Analysis) 
 

Endpoint Docetaxel + 
Cis + 5-FU 

n = 177 

Cis + 5-FU 
 

n = 181 
Median progression free survival (months) 
(95% CI) 

11.4 
(10.1-14.0)

8.3 
(7.4-9.1)

Adjusted hazard ratio 
(95% CI) 
*p-value 

0.70 
(0.55-0.89) 

0.0042 
Median survival (months) 
(95% CI) 

18.6 
(15.7-24.0)

14.5 
(11.6-18.7)

Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.56-0.93) 

0.0128 
Best overall response to chemotherapy (%) 
(95% CI) 

67.8 
(60.4-74.6)

53.6 
(46.0-61.0)

***p-value 0.006 
Best overall response to study treatment 
[chemotherapy +/- radiotherapy] (%) 
(95% CI) 

 
72.3 

(65.1-78.8)

 
58.6 

(51.0-65.8)
***p-value 0.006 
Median duration of response to chemotherapy  
radiotherapy (months) 
(95% CI) 

n = 128 
15.7 

(13.4-24.6) 

n = 106 
11.7 

(10.2-17.4) 
Hazard ratio 
(95% CI) 
**p-value 

0.72 
(0.52-0.99) 

0.0457 
A hazard ratio of less than 1 favours docetaxel + cisplatin + 5-FU 
*Cox model (adjustment for Primary tumour site, T and N clinical stages and PSWHO) 
**Log rank test 
*** Chi-square test 

 
Quality of life parameters 
 
Patients treated with TPF experienced significantly less deterioration of their Global health score 
compared to those treated with PF (p = 0.01, using the EORTC QLQ-C30 scale).  
 
Clinical benefit parameters 



135 

 
The performance status scale, for head and neck (PSS-HN) subscales designed to measure 
understandability of speech, ability to eat in public, and normalcy of diet, was significantly in favour 
of TPF as compared to PF. 
Median time to first deterioration of WHO performance status was significantly longer in the TPF arm 
compared to PF. Pain intensity score improved during treatment in both groups indicating adequate 
pain management. 
 
 Induction chemotherapy followed by chemoradiotherapy (TAX324) 
The safety and efficacy of docetaxel in the induction treatment of patients with locally advanced 
squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a randomised, multi-centre 
open-label, phase III study (TAX324). In this study, 501 patients, with locally advanced SCCHN, and 
a WHO performance status of 0 or 1, were randomised to one of two arms. The study population 
comprised patients with technically unresectable disease, patients with low probability of surgical cure 
and patients aiming at organ preservation. The efficacy and safety evaluation solely addressed survival 
endpoints and the success of organ preservation was not formally addressed. Patients on the docetaxel 
arm received docetaxel (T) 75 mg/m² by intravenous infusion on day 1 followed by cisplatin (P) 
100 mg/m² administered as a 30-minute to three-hour intravenous infusion, followed by the continuous 
intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 4. The cycles were 
repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to receive 
chemoradiotherapy (CRT) as per protocol (TPF/CRT). Patients on the comparator arm received 
cisplatin (P) 100 mg/m² as a 30-minute to three-hour intravenous infusion on day 1 followed by the 
continuous intravenous infusion of 5-fluorouracil (F) 1000 mg/m²/day from day 1 to day 5. The cycles 
were repeated every 3 weeks for 3 cycles. All patients who did not have progressive disease were to 
receive CRT as per protocol (PF/CRT).  
Patients in both treatment arms were to receive 7 weeks of CRT following induction chemotherapy 
with a minimum interval of 3 weeks and no later than 8 weeks after start of the last cycle (day 22 to 
day 56 of last cycle). During radiotherapy, carboplatin (AUC 1.5) was given weekly as a one-hour 
intravenous infusion for a maximum of 7 doses. Radiation was delivered with megavoltage equipment 
using once daily fractionation (2 Gy per day, 5 days per week for 7 weeks, for a total dose of 
70-72 Gy). Surgery on the primary site of disease and/or neck could be considered at any time 
following completion of CRT. All patients on the docetaxel-containing arm of the study received 
prophylactic antibiotics. The primary efficacy endpoint in this study, overall survival (OS) was 
significantly longer (log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF 
(median OS: 70.6 versus 30.1 months respectively), with a 30% risk reduction in mortality compared 
to PF (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.54-0.90) with an overall median 
follow up time of 41.9 months. The secondary endpoint, PFS, demonstrated a 29% risk reduction of 
progression or death and a 22 month improvement in median PFS (35.5 months for TPF and 13.1 for 
PF). This was also statistically significant with an HR of 0.71; 95% CI 0.56-0.90; log-rank test 
p = 0.004. Efficacy results are presented in the table below: 
 



136 

Efficacy of docetaxel in the induction treatment of patientswith locally advanced SCCHN (Intent-to-
Treat Analysis) 
 

Endpoint Docetaxel + Cis + 5-FU 
n = 255 

Cis + 5-FU 
n = 246 

Median overall survival (months)  
(95% CI) 

70.6 
(49.0-NA)

30.1 
(20.9-51.5) 

Hazard ratio: 
(95% CI) 
*p-value  

0.70 
(0.54-0.90) 

0.0058
Median PFS (months)  
(95% CI) 

35.5 
(19.3-NA)

13.1 
(10.6 - 20.2) 

Hazard ratio: 
(95% CI) 
**p-value  

0.71 
(0.56 - 0.90) 

0.004
Best overall response (CR + PR) to 
chemotherapy (%) 
(95% CI) 

71.8 
(65.8-77.2) 

64.2 
(57.9-70.2) 

***p-value 0.070
Best overall response (CR + PR) to study 
treatment [chemotherapy +/- 
chemoradiotherapy] (%) 
(95%CI) 

76.5 
(70.8-81.5) 

71.5 
(65.5-77.1) 

***p-value 0.209
A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil 
*un-adjusted log-rank test 
**un-adjusted log-rank test, not adjusted for multiple comparisons 
***Chi square test, not adjusted for multiple comparisons 
NA-not applicable 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Docetaxel Zentiva in all subsets of the paediatric population in breast cancer, non-small cell lung 
cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less 
differentiated nasopharyngeal carcinoma (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 
20-115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent 
with a three-compartment pharmacokinetic model with half-lives for the ,  and  phases of 4 min, 
36 min and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel 
from the peripheral compartment.  
 
Distribution 
 
Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma 
level of 3.7 µg/ml was obtained with a corresponding AUC of 4.6 h.µg/ml. Mean values for total body 
clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 
individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 
bound to plasma proteins. 
 



137 

Elimination 
 
A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 
both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 
ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 
the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 
excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 
and very low amounts of unchanged medicinal product. 
 
Special populations 
 
Age and gender 
A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 
Pharmacokinetic parameters estimated by the model were very close to those estimated from phase I 
studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient.  
 
Hepatic impairment 
In a small number of patients (n = 23) with clinical chemistry data suggestive of mild to moderate liver 
function impairment (ALT, AST  1.5 times the ULN associated with alkaline phosphatase 
 2.5 times the ULN), total clearance was lowered by 27% on average (see section 4.2).  
 
Fluid retention 
Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 
no data available in patients with severe fluid retention. 
 
Combination therapy 
 
Doxorubicin 
When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 
levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 
and cyclophosphamide were not influenced by their co-administration. 
 
Capecitabine 
Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa 
showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 
effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5’-DFUR. 
 
Cisplatin 
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 
similar to that observed with cisplatin alone. 
 
Cisplatin and 5-fluorouracil 
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 
tumours had no influence on the pharmacokinetics of each individual medicinal product. 
 
Prednisone and dexamethasone 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 
dexamethasone premedication has been studied in 42 patients.  
 
Prednisone 
No effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
5.3 Preclinical safety data 
 
The carcinogenic potential of docetaxel has not been studied. 
 



138 

Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 
test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 
mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 
with the pharmacological activity of docetaxel. 
 
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair 
male fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polysorbate 80 
Ethanol anhydrous 
Citric acid 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf-life 
 
Unopened vial 
3 years 
 
After opening of the vial 
Each vial is for single use and should be used immediately after opening. If not used immediately, 
in-use storage times and conditions are the responsibility of the user.  
 
Once added to the infusion bag  
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions and the medicinal product should be used immediately. If not used immediately, in-use 
storage times and conditions are the responsibility of the user. 
 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 
25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 
intravenous administration).  
 
In addition, physical and chemical in-use stability of the infusion solution prepared as recommended 
has been demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C.  
Store in the original package in order to protect from light. 
 
For storage conditions of the diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
15 ml clear glass (type I) vial with a blue aluminium seal and blue plastic flip-off cap containing 8 ml 
of concentrate. 



139 

 
Each box contains one vial. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Zentiva is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Zentiva solutions. The use of gloves is 
recommended. 
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If Docetaxel Zentiva concentrate or infusion 
solution should come into contact with mucous membranes, wash immediately and thoroughly with 
water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 160 mg/8 ml concentrate for solution for 
infusion, which contains only 1 vial). 
 
Docetaxel Zentiva 160 mg/8 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution. 
 
Each vial is of single use and should be used immediately. 
 
If the vials are stored under refrigeration, allow the required number of boxes of Docetaxel Zentiva 
concentrate for solution for infusion to stand below 25°C for 5 minutes before use. 
More than one vial of Docetaxel Zentiva concentrate for solution for infusion may be necessary to 
obtain the required dose for the patient. Aseptically withdraw the required amount of Docetaxel 
Zentiva concentrate for solution for infusion using a calibrated syringe fitted with a 21G needle. 
 
In Docetaxel Zentiva 160 mg/8 ml vial the concentration of docetaxel is 20 mg/ml. 
The required volume of Docetaxel Zentiva concentrate for solution for infusion must be injected via a 
single injection (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose solution 
or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 
that a concentration of 0.74 mg/ml docetaxel is not exceeded.  
 
Mix the infusion bag or bottle manually using a rocking motion. 
 
The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 
to the patient. 
 
As with all parenteral products, Docetaxel Zentiva infusion solution should be visually inspected prior 
to use, solutions containing a precipitate should be discarded. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
 Zentiva k.s., U kabelovny 130, 102 37 Prague 10, Czech Republic 



140 

 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 April 2007 
Date of last renewal: 20 April 2012  
 
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.  



141 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

ANNEX II 
 

A. MANUFACTURER 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 

 



142 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 
65926 Frankfurt am Main 
Germany  
 
 
 
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 (PSURs) 
 
The marketing authorisation holder shall submit PSUR for this product in accordance with the 
requirements set out in the list of Union reference dates (EURD list) provided for under Article 
107c(7) of Directive 2001/83/EC and  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 marketing authorisation holder (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.  

 

An updated RMP shall be submitted by 31 October 2019. 



143 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



144 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



145 

 
PARTICULARS TO APPEAR ON OUTER PACKAGING  
OUTER CARTON / Docetaxel Zentiva 20 mg/1 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel as trihydrate. 
 
One vial of 1 ml of concentrate contains 20 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information) and citric acid.. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Ready to add to infusion solution. 
CAUTION: Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial 
and add it directly into the infusion solution. See accompanying preparation guide. 
 
Single-use vial. 
 
Read the package leaflet before use. 
 
Intravenous use 
 
 
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 
To be administered under the supervision of a physician experienced in the use of cytotoxic agents. 
 



146 

 
8. EXPIRY DATE 
 
EXP: 
 
Shelf life in infusion bag: see the leaflet. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Discard unused contents appropriately in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/003 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable  
 



147 

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable.



148 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL / Docetaxel Zentiva 20 mg/1 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Zentiva 20 mg/1 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Contains anhydrous ethanol (see leaflet)



149 

 
PARTICULARS TO APPEAR ON OUTER PACKAGING 
 
OUTER CARTON / Docetaxel Zentiva 80 mg/4 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel as trihydrate. 
 
One vial of 4 ml of concentrate contains 80 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information) and citric acid.  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Ready to add to infusion solution. 
CAUTION: Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial 
and add it directly into the infusion solution. See accompanying preparation guide. 
 
Single-use vial. 
 
Read the package leaflet before use. 
 
Intravenous use 
 
 
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 
To be administered under the supervision of a physician experienced in the use of cytotoxic agents. 
 



150 

 
8. EXPIRY DATE 
 
EXP: 
 
Shelf life in infusion bag: see the leaflet. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Discard unused contents appropriately in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable  
 



151 

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 



152 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL / Docetaxel Zentiva 80 mg/4 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Zentiva 80 mg/4 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Contains anhydrous ethanol (see leaflet)



153 

 
PARTICULARS TO APPEAR ON OUTER PACKAGING 
 
OUTER CARTON / Docetaxel Zentiva 160 mg/8 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Docetaxel Zentiva 160 mg/8 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel as trihydrate. 
 
One vial of 8 ml of concentrate contains 160 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information) and citric acid.  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Ready to add to infusion solution. 
CAUTION: Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial 
and add it directly into the infusion solution. See accompanying preparation guide. 
 
Single-use vial. 
 
Read the package leaflet before use. 
 
Intravenous use 
 
 
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 
To be administered under the supervision of a physician experienced in the use of cytotoxic agents. 
 
 



154 

8. EXPIRY DATE 
 
EXP: 
 
Shelf life in infusion bag: see the leaflet. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Discard unused contents appropriately in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 
 
 
12. MARKETING AUTHORISATION NUMBER 
 
EU/1/07/384/005 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE  
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable  
 
 



155 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable.



156 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL / Docetaxel Zentiva 160 mg/8 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Zentiva 160 mg/8 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Contains anhydrous ethanol (see leaflet)



157 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



158 

 
Package leaflet: Information for the patient 

Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion 
docetaxel 

 
 
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, your hospital pharmacist or nurse. 
- If you get any side effects, talk to your doctor, hospital pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Docetaxel Zentiva is and what it is used for 
2. What you need to know before you use Docetaxel Zentiva 
3. How to use Docetaxel Zentiva 
4. Possible side effects 
5. How to store Docetaxel Zentiva 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Zentiva is and what it is used for  
 
The name of this medicine is Docetaxel Zentiva. Its common name is docetaxel. Docetaxel is a 
substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Zentiva has been prescribed by your doctor for the treatment of breast cancer, special forms 
of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck cancer:  
- For the treatment of advanced breast cancer, Docetaxel Zentiva could be administered either alone or 
in combination with doxorubicin, or trastuzumab, or capecitabine. 
- For the treatment of early breast cancer with or without lymph node involvement, Docetaxel Zentiva 
could be administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, Docetaxel Zentiva could be administered either alone or in 
combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Zentiva is administered in combination with 
prednisone or prednisolone. 
- For the treatment of metastatic gastric cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
- For the treatment of head and neck cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Zentiva 
 
You must not be given Docetaxel Zentiva: 
 
 if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Zentiva (listed in section 6). 
 if the number of white blood cells is too low. 
 if you have a severe liver disease. 
 



159 

Warnings and precautions 
 
Before each treatment with Docetaxel Zentiva, you will have blood tests to check that you have 
enough blood cells and sufficient liver function to receive Docetaxel Zentiva. In case of white blood 
cells disturbances, you may experience associated fever or infections. 
 
Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 
diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 
serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 
 
Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision 
problems, in particular blurred vision, you should immediately have your eyes and vision examined.  
 
Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 
paclitaxel therapy. 
 
Tell your doctor, hospital pharmacist or nurse if you have heart problems.  
 
If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 
please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 
treatment immediately. 
 
You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 
one day prior to Docetaxel Zentiva administration and to continue for one or two days after it in order 
to minimise certain undesirable effects which may occur after the infusion of Docetaxel Zentiva in 
particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain). 
 
During treatment, you may be given other medicines to maintain the number of your blood cells. 
 
Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 
Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with Docetaxel Zentiva:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 
may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 
doctor or healthcare professional. 
 
Docetaxel Zentiva contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, 
epilepsy or liver impairment. See also section “Docetaxel Zentiva contains ethanol (alcohol)” below. 
 
Other medicines and Docetaxel Zentiva 
 
Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 
medicine, including medicines obtained without a prescription. This is because Docetaxel Zentiva or 
the other medicine may not work as well as expected and you may be more likely to get a side effect. 
The amount of alcohol in this medicinal product may alter the effects of other medicines. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Zentiva must NOT be administered if you are pregnant unless clearly indicated by your 
doctor.  
 



160 

You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy, because Docetaxel Zentiva may be harmful for the unborn baby. If 
pregnancy occurs during your treatment, you must immediately inform your doctor. 
 
 
You must not breast-feed while you are treated with Docetaxel Zentiva. 
 
If you are a man being treated with Docetaxel Zentiva 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 
docetaxel may alter male fertility. 
 
Driving and using machines 
 
The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 
You may experience side effects of this medicine that may impair your ability to drive, use tools or 
operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 
machines before discussing with your doctor, nurse or hospital pharmacist. 
 
Docetaxel Zentiva contains ethanol (alcohol)  
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol 
anhydrous  per vial, equivalent to 10 ml of beer or 4 ml wine. 
 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 
as patients with liver disease, or epilepsy. 
 
The amount of alcohol in this medicinal product may have effects on the central nervous system (the 
part of the nervous system that includes the brain and spinal cord). 
 
 
3. How to use Docetaxel Zentiva 
 
Docetaxel Zentiva will be administered to you by a healthcare professional. 
 
Usual dose 
 
The dose will depend on your weight and your general condition. Your doctor will calculate your body 
surface area in square meters (m²) and will determine the dose you should receive.  
 
Method and route of administration 
 
Docetaxel Zentiva will be given by infusion into one of your veins (intravenous use). The infusion will 
last approximately one hour during which you will be in the hospital. 
 
Frequency of administration 
 
You should usually receive your infusion once every 3 weeks. 
 
Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 
condition and your response to Docetaxel Zentiva. In particular, please inform your doctor in case of 
diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him results 
of your blood tests. Such information will allow her/him to decide whether a dose reduction is needed. 
If you have any further questions on the use of this medicine, ask your doctor, or hospital pharmacist. 
 
 
4. Possible side effects 



161 

 
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. 
 
 
The most commonly reported adverse reactions of Docetaxel Zentiva alone are: decrease in the 
number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 
diarrhoea and tiredness. 
 
The severity of adverse events of Docetaxel Zentiva may be increased when Docetaxel Zentiva is 
given in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people):  
 flushing, skin reactions, itching 
 chest tightness; difficulty in breathing  
 fever or chills 
 back pain  
 low blood pressure. 
More severe reactions may occur. 
If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 
which may be more severe. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Zentiva the following may occur, and the frequency may vary with 
the combinations of medicines that are received: 
 
Very common (may affect more than 1 in 10 people): 
 infections, decrease in the number of red (anaemia), or white blood cells (which are important in 

fighting infection) and platelets 
 fever: if this happens you must tell your doctor immediately 
 allergic reactions as described above 
 loss of appetite (anorexia)  
 insomnia 
 feeling of numbness or pins and needles or pain in the joints or muscles 
 headache  
 alteration in sense of taste  
 inflammation of the eye or increased tearing of the eyes  
 swelling caused by faulty lymphatic drainage 
 shortness of breath  
 nasal drainage; inflammation of the throat and nose; cough 
 bleeding from the nose  
 sores in the mouth  
 stomach upsets including nausea, vomiting and diarrhoea, constipation 
 abdominal pain 
 indigestion 
 hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 

permanent hair loss has been observed 
 redness and swelling of the palms of your hands or soles of your feet which may cause your skin 

to peel (this may also occur on the arms, face, or body) 
 change in the colour of your nails, which may detach  



162 

 muscle aches and pains; back pain or bone pain 
 change or absence of menstrual period 
 swelling of the hands, feet, legs  
 tiredness; or flu-like symptoms 
 weight gain or loss. 
 infection of the upper respiratory tract. 
 
Common (may affect up to 1 in 10 people): 
 oral candidiasis 
 dehydration 
 dizziness 
 hearing impaired 
 decrease in blood pressure; irregular or rapid heart beat 
 heart failure 
 oesophagitis  
 dry mouth 
 difficulty or painful swallowing 
 haemorrhage 
 raised liver enzymes (hence the need for regular blood tests) 
 rises in blood sugar levels (diabetes) 
 decrease of the potassium, calcium and/or phosphate in your blood.  
 
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 blood clots. 
 acute myeloid leukaemia and myelodysplastic syndrome (types of blood cancer) may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 
Rare (may affect up to 1 in 1,000 people): 
 inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 

perforation. 
 
Frequency not known (cannot be stimated from available data): 
 interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 
 pneumonia (infection of the lungs) 
 pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath). 
 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders) 
 ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 
this happens, you must tell your doctor immediately 

 injection site reactions at the site of a previous reaction. 
 non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, peeling or 

bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) 
with or without a rash. You may also have flu-like symptoms at the same time, such as fever, 
chills or aching muscles.) 

 Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with bumps 
under the swollen skin (including your skin folds, trunk, and upper extremities) and blisters 
accompanied by fever.) 



163 

 
Reporting of adverse effects 
If you get any side effects , talkto your doctor, hospital 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 Docetaxel Zentiva 
 
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 vial after EXP. The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
Use the vial immediately after its opening. If not used immediately, in-use storage times and 
conditions are the responsibility of the user. 
 
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions. 
 
Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 
storage times and conditions are the responsibility of the user and would normally not be longer than 
6 hours below 25°C including the one hour infusion. 
 
Physical and chemical in-use stability of the infusion solution prepared as recommended has been 
demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded. 
 
 Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Docetaxel Zentiva contains 
- The active substance is docetaxel (as trihydrate). Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel.  
- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and citric acid. 
 
What Docetaxel Zentiva looks like and contents of the pack 
Docetaxel Zentiva concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a 7 ml clear colourless glass vial with a green aluminium seal and a 
green plastic flip-off cap. 
 
Each box contains one vial of 1 ml concentrate (20 mg docetaxel). 
 
Marketing Authorisation Holder  
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 



164 

 
Manufacturer(s) 
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 
Zentiva, k.s. 
Tél/Tel: +32 280 86 420 
PV-Belgium@zentiva.com 
 

Lietuva 
Zentiva, k.s. 
Tel: +370 52152025 
PV-Lithuania@zentiva.com 

България 
Zentiva, k.s. 
Тел: + 359 2 805 72 08 
PV-Bulgaria@zentiva.com 
 

Luxembourg/Luxemburg 
Zentiva, k.s. 
Tél/Tel: +352 208 82330 
PV-Luxembourg@zentiva.com 

Česká republika 
Zentiva, k.s. 
Tel: +420 267 241 111 
PV-Czech-Republic@zentiva.com 

Magyarország 
Zentiva, k.s. 
Tel.: +36 165 55 722 
PV-Hungary@zentiva.com 

Danmark 
Zentiva, k.s. 
Tlf: +45 787 68 400 
PV-Denmark@zentiva.com 
 

Malta 
Zentiva, k.s. 
Tel: +356 277 82 052 
PV-Malta@zentiva.com 

Deutschland 
Zentiva Pharma GmbH  
Tel: +49 (0) 800 53 53 010 
PV-Germany@zentiva.com 
 

Nederland 
Zentiva, k.s. 
Tel: +31 202 253 638 
PV-Netherlands@zentiva.com 

Eesti 
Zentiva, k.s. 
Tel: +372 52 70308 
PV-Estonia@zentiva.com 
 

Norge 
Zentiva, k.s. 
Tlf: +47 219 66 203 
PV-Norway@zentiva.com 

Ελλάδα 
Zentiva, k.s. 
Τηλ: +30 211 198 7510 
PV-Greece@zentiva.com 
 

Österreich 
Zentiva, k.s. 
Tel: +43 720 778 877 
PV-Austria@zentiva.com 

España 
Zentiva, k.s. 
Tel: +34 931 815 250 
PV-Spain@zentiva.com 
 

Polska 
Zentiva Polska Sp. z o.o. 
Tel: + 48 22 375 92 00 
PV-Poland@zentiva.com 

France 
Zentiva France 
Tél: +33 (0) 800 089 219  

Portugal 
Zentiva Portugal, Lda 
Tel: +351210601360



165 

PV-France@zentiva.com 
 

PV-Portugal@zentiva.com 

Hrvatska 
Zentiva, k.s. 
Tel: +385 155 17 772 
PV-Croatia@zentiva.com 
 
Ireland 
Zentiva, k.s. 
Tel: +353 766 803 944 
PV-Ireland@zentiva.com 
 

România 
S.C. ZENTIVA S.A. 
Tel:  +40 021 304 7597 
PV-Romania@zentiva.com 
 
Slovenija 
Zentiva, k.s. 
Tel: +386 360 00 408 
PV-Slovenia@zentiva.com 

Ísland 
Zentiva, k.s. 
Sími: +354 539 0650 
PV-Iceland@zentiva.com 
 

Slovenská republika 
Zentiva, a.s. 
Tel: +421 2 3918 3010 
PV-Slovakia@zentiva.com 

Italia 
Zentiva Italia S.r.l. 
 +39-02-38598801 
PV-Italy@zentiva.com 

Suomi/Finland 
Zentiva, k.s. 
Puh/Tel: +358 942 598 648 
PV-Finland@zentiva.com 

Κύπρος 
Zentiva, k.s. 
Τηλ: +357 240 30 144 
PV-Cyprus@zentiva.com 
 

Sverige 
Zentiva, k.s. 
Tel: +46 840 838 822 
PV-Sweden@zentiva.com 

Latvija 
Zentiva, k.s. 
Tel: +371 67893939 
PV-Latvia@zentiva.com 

United Kingdom 
Zentiva Pharma UK Limited 
Tel: +44 (0) 845 372 7101 
PV-United-Kingdom@zentiva.com 

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



166 

The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL ZENTIVA 20 mg/1 ml 
CONCENTRATE FOR SOLUTION FOR INFUSION 
 
 
It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 
Zentiva infusion solution. 
 
Recommendations for the safe handling 
Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing its solutions. The use of gloves is recommended.  
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If it should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation of the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion, 
which contains only 1 vial). 
 
Docetaxel Zentiva 20 mg/1 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution.  
 Each vial is for single use and should be used immediately after opening. If not used 

immediately, in-use storage times and conditions are the responsibility of the user. More than 
one vial of concentrate for solution for infusion may be necessary to obtain the required dose for 
the patient. For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate 
for solution. 

 Aseptically withdraw the required amount of concentrate for solution for infusion with a 
calibrated syringe fitted with a 21G needle. 

In Docetaxel Zentiva 20 mg/1 ml vial the concentration of docetaxel is 20 mg/ml. 
 Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing 

either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose 
greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that 
a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 Mix the infusion bag or bottle manually using a rocking motion. 
 From a microbiological point of view, reconstitution /dilution must take place in controlled and 

aseptic conditions and the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user. 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored 
below 25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour 
infusion intravenous administration).  
In addition, physical and chemical in-use stability of the infusion solution prepared as 
recommended has been demonstrated in non-PVC bags up to 48 hours when stored between 2°C 
to 8°C.  
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 
appear, the solution must no longer be used and shall be discarded. 

 As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 
Disposal 
All materials that have been utilised for dilution and administration should be disposed of according to 
standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.  



167 

Package leaflet: Information for the patient 
 

Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion 
docetaxel 

 
 
Read all of this leaflet carefully before you start using this medicine becsue 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, your hospital pharmacist or nurse. 
- If you get any side effects talk to your doctor, hospital pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Docetaxel Zentiva is and what it is used for 
2. What you need to know before you use Docetaxel Zentiva 
3. How to use Docetaxel Zentiva 
4. Possible side effects 
5. How to store Docetaxel Zentiva 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Zentiva is and what it is used for  
 
The name of this medicine is Docetaxel Zentiva. Its common name is docetaxel. Docetaxel is a 
substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Zentiva has been prescribed by your doctor for the treatment of breast cancer, special forms 
of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck cancer:  
- For the treatment of advanced breast cancer, Docetaxel Zentiva could be administered either alone or 
in combination with doxorubicin, or trastuzumab, or capecitabine. 
- For the treatment of early breast cancer with or without lymph node involvement, Docetaxel Zentiva 
could be administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, Docetaxel Zentiva could be administered either alone or in 
combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Zentiva is administered in combination with 
prednisone or prednisolone. 
- For the treatment of metastatic gastric cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
- For the treatment of head and neck cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Zentiva 
 
You must not be given Docetaxel Zentiva:  
 
 if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Zentiva (listed in section 6). 
 if the number of white blood cells is too low. 
 if you have a severe liver disease. 
 



168 

Warnings and precautions 
 
Before each treatment with Docetaxel Zentiva, you will have blood tests to check that you have 
enough blood cells and sufficient liver function to receive Docetaxel Zentiva. In case of white blood 
cells disturbances, you may experience associated fever or infections. 
 
Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 
diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 
serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 
 
Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision 
problems, in particular blurred vision, you should immediately have your eyes and vision examined.  
 
Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 
paclitaxel therapy. 
 
Tell your doctor, hospital pharmacist or nurse if you have heart problems.  
 
If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 
please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 
treatment immediately. 
 
You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 
one day prior to Docetaxel Zentiva administration and to continue for one or two days after it in order 
to minimise certain undesirable effects which may occur after the infusion of Docetaxel Zentiva in 
particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain). 
 
During treatment, you may be given other medicines to maintain the number of your blood cells. 
 
Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 
Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with Docetaxel Zentiva:  

- SJS/TEN symptoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 
may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 
doctor or healthcare professional. 
 
Docetaxel Zentiva contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, 
epilepsy or liver impairment. See also section “Docetaxel Zentiva contains ethanol (alcohol)” below. 
 
Other medicines and Docetaxel Zentiva 
 
Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 
medicine, including medicines obtained without a prescription. This is because Docetaxel Zentiva or 
the other medicine may not work as well as expected and you may be more likely to get a side effect.  
The amount of alcohol in this medicinal product may alter the effects of other medicines. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Zentiva must NOT be administered if you are pregnant unless clearly indicated by your 
doctor.  
 



169 

You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy , because Docetaxel Zentiva may be harmful for the unborn baby. If 
pregnancy occurs during your treatment, you must immediately inform your doctor. 
 
You must not breast-feed while you are treated with Docetaxel Zentiva. 
 
If you are a man being treated with Docetaxel Zentiva 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 
docetaxel may alter male fertility. 
 
Driving and using machines 
 
The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 
You may experience side effects of this medicine that may impair your ability to drive, use tools or 
operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 
machines before discussing with your doctor, nurse or hospital pharmacist. 
 
Docetaxel Zentiva contains ethanol (alcohol) 
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1.58 g ethanol 
anhydrous   per vial, equivalent to 40 ml of beer or 17 ml wine. 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 
as patients with liver disease, or epilepsy. 
 
The amount of alcohol in this medicinal product may have effects on the central nervous system (the 
part of the nervous system that includes the brain and spinal cord). 
 
 
3. How to use Docetaxel Zentiva 
 
Docetaxel Zentiva will be administered to you by a healthcare professional. 
 
Usual dose 
 
The dose will depend on your weight and your general condition. Your doctor will calculate your body 
surface area in square meters (m²) and will determine the dose you should receive.  
 
Method and route of administration 
 
Docetaxel Zentiva will be given by infusion into one of your veins (intravenous use). The infusion will 
last approximately one hour during which you will be in the hospital. 
 
Frequency of administration 
 
You should usually receive your infusion once every 3 weeks. 
 
Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 
condition and your response to Docetaxel Zentiva. In particular, please inform your doctor in case of 
diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him results 
of your blood tests. Such information will allow her/him to decide whether a dose reduction is needed. 
If you have any further questions on the use of this medicine, ask your doctor, or hospital pharmacist. 
 
 
4. Possible side effects  
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 



170 

 
Your doctor will discuss these with you and will explain the potential risks and benefits of your 
treatment. 
 
The most commonly reported adverse reactions of Docetaxel Zentiva alone are: decrease in the 
number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 
diarrhoea and tiredness. 
 
The severity of adverse events of Docetaxel Zentiva may be increased when Docetaxel Zentiva is 
given in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions may occur (may affect more than 
1 in 10 people):  
 flushing, skin reactions, itching 
 chest tightness; difficulty in breathing  
 fever or chills 
 back pain  
 low blood pressure. 
More severe reactions may occur. 
If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 
which may be more severe. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Zentiva the following may occur, and the frequency may vary with 
the combinations of medicines that are received 
 
Very common (may affect more than 1 in 10 people): 
 infections, decrease in the number of red (anaemia), or white blood cells (which are important in 

fighting infection) and platelets 
 fever: if this happens you must tell your doctor immediately 
 allergic reactions as described above 
 loss of appetite (anorexia)  
 insomnia 
 feeling of numbness or pins and needles or pain in the joints or muscles 
 headache  
 alteration in sense of taste  
 inflammation of the eye or increased tearing of the eyes  
 swelling caused by faulty lymphatic drainage 
 shortness of breath  
 nasal drainage; inflammation of the throat and nose; cough 
 bleeding from the nose  
 sores in the mouth  
 stomach upsets including nausea, vomiting and diarrhoea, constipation 
 abdominal pain 
 indigestion 
 hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 

permanent hair loss has been observed 
 redness and swelling of the palms of your hands or soles of your feet which may cause your skin 

to peel (this may also occur on the arms, face, or body) 
 change in the colour of your nails, which may detach  
 muscle aches and pains; back pain or bone pain 
 change or absence of menstrual period 
 swelling of the hands, feet, legs  



171 

 tiredness; or flu-like symptoms 
 weight gain or loss. 
 infection of the upper respiratory tract. 
 
Common (may affect up to 1 in 10 people): 
 oral candidiasis 
 dehydration 
 dizziness 
 hearing impaired 
 decrease in blood pressure; irregular or rapid heart beat 
 heart failure 
 oesophagitis  
 dry mouth 
 difficulty or painful swallowing 
 haemorrhage 
 raised liver enzymes (hence the need for regular blood tests) 
 rises in blood sugar levels (diabetes) 
 decrease of the potassium, calcium and/or phosphate in your blood.  
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 blood clots. 
 acute myeloid leukaemia and myelodysplastic syndrome (types of blood cancer) may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 
Rare (may affect up to 1 in 1,000 people): 
 inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 

perforation. 
 
Frequency not known (cannot be estimated from the available data): 
 interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 
 pneumonia (infection of the lungs) 
 pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath) 
 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders) 
 ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 
this happens, you must tell your doctor immediately 

 injection site reactions at the site of a previous reaction. 
 non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, peeling or 

bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) 
with or without a rash. You may also have flu-like symptoms at the same time, such as fever, 
chills or aching muscles.) 

 Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with bumps 
under the swollen skin (including your skin folds, trunk, and upper extremities) and blisters 
accompanied by fever.) 

 
Reporting of adverse effects 
If you get any side effects talk to your doctor, hospital 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 



172 

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 Docetaxel Zentiva 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on outer carton and on the label of the 
vial after EXP. The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
Use the vial immediately after its opening. If not used immediately, in-use storage times and 
conditions are the responsibility of the user.  
 
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions. 
 
Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 
storage times and conditions are the responsibility of the user and would normally not be longer than 
6 hours below 25°C including the one hour infusion.  
 
Physical and chemical in-use stability of the infusion solution prepared as recommended has been 
demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded. 
 
 Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
you no longer use. These measures will help protect the environment. 
 
6. Contents of the pack and other information 
 
What Docetaxel Zentiva contains 
- The active substance is docetaxel (as trihydrate). Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel.  
- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and citric acid. 
 
What Docetaxel Zentiva looks like and contents of the pack 
Docetaxel Zentiva concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a 7 ml clear colourless glass vial with a magenta aluminium seal and a 
magenta plastic flip-off cap. 
 
Each box contains one vial of 4 ml concentrate (80 mg docetaxel). 
 
Marketing Authorisation Holder 
 
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 
 
Manufacturer(s) 
Sanofi-Aventis GmbH 
Industriepark Höchst 



173 

65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
België/Belgique/Belgien 
Zentiva, k.s. 
Tél/Tel: +32 280 86 420 
PV-Belgium@zentiva.com 
 

Lietuva 
Zentiva, k.s. 
Tel: +370 52152025 
PV-Lithuania@zentiva.com 

България 
Zentiva, k.s. 
Тел: + 359 2 805 72 08 
PV-Bulgaria@zentiva.com 
 

Luxembourg/Luxemburg 
Zentiva, k.s. 
Tél/Tel: +352 208 82330 
PV-Luxembourg@zentiva.com 

Česká republika 
Zentiva, k.s. 
Tel: +420 267 241 111 
PV-Czech-Republic@zentiva.com 

Magyarország 
Zentiva, k.s. 
Tel.: +36 165 55 722 
PV-Hungary@zentiva.com 

Danmark 
Zentiva, k.s. 
Tlf: +45 787 68 400 
PV-Denmark@zentiva.com 
 

Malta 
Zentiva, k.s. 
Tel: +356 277 82 052 
PV-Malta@zentiva.com 

Deutschland 
Zentiva Pharma GmbH  
Tel: +49 (0) 800 53 53 010 
PV-Germany@zentiva.com 
 

Nederland 
Zentiva, k.s. 
Tel: +31 202 253 638 
PV-Netherlands@zentiva.com 

Eesti 
Zentiva, k.s. 
Tel: +372 52 70308 
PV-Estonia@zentiva.com 
 

Norge 
Zentiva, k.s. 
Tlf: +47 219 66 203 
PV-Norway@zentiva.com 

Ελλάδα 
Zentiva, k.s. 
Τηλ: +30 211 198 7510 
PV-Greece@zentiva.com 
 

Österreich 
Zentiva, k.s. 
Tel: +43 720 778 877 
PV-Austria@zentiva.com 

España 
Zentiva, k.s. 
Tel: +34 931 815 250 
PV-Spain@zentiva.com 
 

Polska 
Zentiva Polska Sp. z o.o. 
Tel: + 48 22 375 92 00 
PV-Poland@zentiva.com 

France 
Zentiva France 
Tél: +33 (0) 800 089 219  
PV-France@zentiva.com 
 

Portugal 
Zentiva Portugal, Lda 
Tel: +351210601360 
PV-Portugal@zentiva.com 

Hrvatska 
Zentiva, k.s. 

România 
S.C. ZENTIVA S.A.



174 

Tel: +385 155 17 772 
PV-Croatia@zentiva.com 
 
Ireland 
Zentiva, k.s. 
Tel: +353 766 803 944 
PV-Ireland@zentiva.com 
 

Tel: +40 021 304 7597 
PV-Romania@zentiva.com 
 
Slovenija 
Zentiva, k.s. 
Tel: +386 360 00 408 
PV-Slovenia@zentiva.com 

Ísland 
Zentiva, k.s. 
Sími: +354 539 0650 
PV-Iceland@zentiva.com 
 

Slovenská republika 
Zentiva, a.s. 
Tel: +421 2 3918 3010 
PV-Slovakia@zentiva.com 

Italia 
Zentiva Italia S.r.l. 
 +39-02-38598801 
PV-Italy@zentiva.com 

Suomi/Finland 
Zentiva, k.s. 
Puh/Tel: +358 942 598 648 
PV-Finland@zentiva.com 

Κύπρος 
Zentiva, k.s. 
Τηλ: +357 240 30 144 
PV-Cyprus@zentiva.com 
 

Sverige 
Zentiva, k.s. 
Tel: +46 840 838 822 
PV-Sweden@zentiva.com 

Latvija 
Zentiva, k.s. 
Tel: +371 67893939 
PV-Latvia@zentiva.com 

United Kingdom 
Zentiva Pharma UK Limited 
Tel: +44 (0) 845 372 7101 
PV-United-Kingdom@zentiva.com 

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



175 

The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL ZENTIVA 80 mg/4 ml 
CONCENTRATE FOR SOLUTION FOR INFUSION 
 
 
It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 
Zentiva infusion solution. 
 
Recommendations for the safe handling 
Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing its solutions. The use of gloves is recommended.  
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If it should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation of the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion, 
which contains only 1 vial). 
 
Docetaxel Zentiva 80 mg/4 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution.  
 Each vial is for single use and should be used immediately after opening. If not used 

immediately, in-use storage times and conditions are the responsibility of the user. More than 
one vial of concentrate for solution for infusion may be necessary to obtain the required dose for 
the patient. For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate 
for solution. 

 Aseptically withdraw the required amount of concentrate for solution for infusion with a 
calibrated syringe fitted with a 21G needle. 

In Docetaxel Zentiva 80 mg/4 ml vial the concentration of docetaxel is 20 mg/ml. 
 Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing 

either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose 
greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that 
a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 Mix the infusion bag or bottle manually using a rocking motion. 
 From a microbiological point of view, reconstitution /dilution must take place in controlled and 

aseptic conditions and the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user. 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored 
below 25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour 
infusion intravenous administration).  
In addition, physical and chemical in-use stability of the infusion solution prepared as 
recommended has been demonstrated in non-PVC bags up to 48 hours when stored between 2°C 
to 8°C.  
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 
appear, the solution must no longer be used and shall be discarded. 

 As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 
Disposal 
All materials that have been utilised for dilution and administration should be disposed of according to 
standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 



176 

 
Package leaflet: Information for the patient 

 
Docetaxel Zentiva 160 mg/8 ml concentrate for solution for infusion 

docetaxel 
 
 
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, your hospital pharmacist or nurse. 
- If you get any side effects talk to your doctor, hospital pharmacist or nurse. This includes any 

possible side effect not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Docetaxel Zentiva is and what it is used for 
2. What you need to know before you use Docetaxel Zentiva 
3. How to use Docetaxel Zentiva 
4. Possible side effects 
5. How to store Docetaxel Zentiva 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Zentiva is and what it is used for  
 
The name of this medicine is Docetaxel Zentiva. Its common name is docetaxel. Docetaxel is a 
substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Zentiva has been prescribed by your doctor for the treatment of breast cancer, special forms 
of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck cancer:  
- For the treatment of advanced breast cancer, Docetaxel Zentiva could be administered either alone or 
in combination with doxorubicin, or trastuzumab, or capecitabine. 
- For the treatment of early breast cancer with or without lymph node involvement, Docetaxel Zentiva 
could be administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, Docetaxel Zentiva could be administered either alone or in 
combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Zentiva is administered in combination with 
prednisone or prednisolone. 
- For the treatment of metastatic gastric cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
- For the treatment of head and neck cancer, Docetaxel Zentiva is administered in combination with 
cisplatin and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Zentiva 
 
You must not be given Docetaxel Zentiva:  
 
 if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Zentiva (listed in section 6). 
 if the number of white blood cells is too low. 
 if you have a severe liver disease. 
 



177 

Warnings and precautions 
 
Before each treatment with Docetaxel Zentiva, you will have blood tests to check that you have 
enough blood cells and sufficient liver function to receive Docetaxel Zentiva. In case of white blood 
cells disturbances, you may experience associated fever or infections. 
 
Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 
diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 
serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately. 
 
Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision problems, 
in particular blurred vision, you should immediately have your eyes and vision examined. 
 
Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 
paclitaxel therapy. 
 
Tell your doctor, hospital pharmacist or nurse if you have heart problems. 
 
If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 
please tell your doctor, hospital pharmacist or nurse immediately. Your doctor may stop your 
treatment immediately. 
 
You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 
one day prior to Docetaxel Zentiva administration and to continue for one or two days after it in order 
to minimise certain undesirable effects which may occur after the infusion of Docetaxel Zentiva in 
particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain). 
 
During treatment, you may be given other medicines to maintain the number of your blood cells. 
 
Severe skin problems such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), 
Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with Docetaxel Zentiva:  

- SJS/TEN sympoms may include blistering, peeling or bleeding on any part of your skin 
(including your lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You 
may also have flu-like symptoms at the same time, such as fever, chills or aching muscles. 

- AGEP symptoms may include a red, scaly widespread rash with bumps under the swollen skin 
(including your skin folds, trunk, and upper extremities) and blisters accompanied by fever.  

If you develop severe skin reactions or any of the reactions listed above, immediately contact your 
doctor or healthcare professional. 
 
Docetaxel Zentiva contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, 
epilepsy or liver impairment. See also section “Docetaxel Zentiva contains ethanol (alcohol)” below. 
 
Other medicines and Docetaxel Zentiva 
 
Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 
medicine, including medicines obtained without a prescription. This is because Docetaxel Zentiva or 
the other medicine may not work as well as expected and you may be more likely to get a side effect. 
The amount of alcohol in this medicinal product may alter the effects of other medicines. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Zentiva must NOT be administered if you are pregnant unless clearly indicated by your 
doctor.  
 



178 

You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy, because Docetaxel Zentiva may be harmful for the unborn baby. If 
pregnancy occurs during your treatment, you must immediately inform your doctor. 
 
 
You must not breast-feed while you are treated with Docetaxel Zentiva. 
 
If you are a man being treated with Docetaxel Zentiva 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 
docetaxel may alter male fertility. 
 
Driving and using machines 
 
The amount of alcohol in this medicinal product may impair your ability to drive or use machines. 
You may experience side effects of this medicine that may impair your ability to drive, use tools or 
operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 
machines before discussing with your doctor, nurse or hospital pharmacist. 
 
Docetaxel Zentiva contains ethanol (alcohol) 
 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3.16 g ethanol 
anhydrous   per vial, equivalent to 80 ml of beer or 33 ml wine. 
Harmful for those suffering from alcoholism.  
To be taken into account in pregnant or breast-feeding women, in children and high-risk groups such 
as patients with liver disease, or epilepsy. 
 
The amount of alcohol in this medicinal product may have effects on the central nervous system (the 
part of the nervous system that includes the brain and spinal cord). 
 
 
3. How to use Docetaxel Zentiva 
 
Docetaxel Zentiva will be administered to you by a healthcare professional. 
 
Usual dose 
 
The dose will depend on your weight and your general condition. Your doctor will calculate your body 
surface area in square meters (m²) and will determine the dose you should receive.  
 
Method and route of administration 
 
Docetaxel Zentiva will be given by infusion into one of your veins (intravenous use). The infusion will 
last approximately one hour during which you will be in the hospital. 
 
Frequency of administration 
 
You should usually receive your infusion once every 3 weeks. 
 
Your doctor may change the dose and frequency of dosing depending on your blood tests, your general 
condition and your response to Docetaxel Zentiva. In particular, please inform your doctor in case of 
diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him results 
of your blood tests. Such information will allow her/him to decide whether a dose reduction is needed. 
If you have any further questions on the use of this medicine, ask your doctor, or hospital pharmacist. 
 
 
4. Possible side effects 
 



179 

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. 
 
The most commonly reported adverse reactions of Docetaxel Zentiva alone are: decrease in the 
number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 
diarrhoea and tiredness. 
 
The severity of adverse events of Docetaxel Zentiva may be increased when Docetaxel Zentiva is 
given in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions may occur (may affect more than 
1 in 10 people):  
 flushing, skin reactions, itching 
 chest tightness; difficulty in breathing  
 fever or chills 
 back pain  
 low blood pressure. 
More severe reactions may occur.  
If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 
which may be more severe. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Zentiva the following may occur, and the frequency may vary with 
the combinations of medicines that are received 
 
Very common (may affect more than 1 in 10 people): 
 infections, decrease in the number of red (anaemia), or white blood cells (which are important in 

fighting infection) and platelets 
 fever: if this happens you must tell your doctor immediately 
 allergic reactions as described above 
 loss of appetite (anorexia)  
 insomnia 
 feeling of numbness or pins and needles or pain in the joints or muscles 
 headache  
 alteration in sense of taste  
 inflammation of the eye or increased tearing of the eyes  
 swelling caused by faulty lymphatic drainage 
 shortness of breath  
 nasal drainage; inflammation of the throat and nose; cough 
 bleeding from the nose  
 sores in the mouth  
 stomach upsets including nausea, vomiting and diarrhoea, constipation 
 abdominal pain 
 indigestion 
 hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 

permanent hair loss has been observed 
 redness and swelling of the palms of your hands or soles of your feet which may cause your skin 

to peel (this may also occur on the arms, face, or body) 
 change in the colour of your nails, which may detach  
 muscle aches and pains; back pain or bone pain 
 change or absence of menstrual period 



180 

 swelling of the hands, feet, legs  
 tiredness; or flu-like symptoms 
 weight gain or loss. 
 infection of the upper respiratory tract. 
 
Common (may affect up to 1 in 10 people): 
 oral candidiasis 
 dehydration 
 dizziness 
 hearing impaired 
 decrease in blood pressure; irregular or rapid heart beat 
 heart failure 
 oesophagitis  
 dry mouth 
 difficulty or painful swallowing 
 haemorrhage 
 raised liver enzymes (hence the need for regular blood tests) 
 rises in blood sugar levels (diabetes) 
 decrease of the potassium, calcium and/or phosphate in your blood.  
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 blood clots. 
 acute myeloid leukaemia and myelodysplastic syndrome (types of blood cancer) may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 
Rare (may affect up to 1 in 1,000 people): 
 inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal 

perforation. 
 
Frequency not known (cannot be estimated from the available data): 
 interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing. 

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 
 pneumonia (infection of the lungs) 
 pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath) 
 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium and/or magnesium in your blood (electrolyte balance disorders) 
 ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

severe shortness of breath, dizziness, and/or fainting). Some of these symptoms can be serious. If 
this happens, you must tell your doctor immediately 

 injection site reactions at the site of a previous reaction. 
 non-Hodgkin lymphoma (a cancer affecting the immune system) and other cancers may occur in 

patients who are treated with docetaxel together with certain other anticancer treatments. 
 Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blistering, peeling or 

bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet) 
with or without a rash. You may also have flu-like symptoms at the same time, such as fever, 
chills or aching muscles.) 

 Acute Generalized Exanthematous Pustulosis (AGEP) (red, scaly widespread rash with bumps 
under the swollen skin (including your skin folds, trunk, and upper extremities) and blisters 
accompanied by fever.) 

 
Reporting of adverse effects  
If you get any side effects talk to your doctor, hospital 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 



181 

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 Docetaxel Zentiva 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on outer carton and on the label of the 
vial after EXP. The expiry date refers to the last day of that month. 
 
Do not store above 25°C. 
Store in the original package in order to protect from light. 
 
Use the vial immediately after its opening. If not used immediately, in-use storage times and 
conditions are the responsibility of the user.  
 
From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions. 
 
Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 
storage times and conditions are the responsibility of the user and would normally not be longer than 
6 hours below 25°C including the one hour infusion.  
 
Physical and chemical in-use stability of the infusion solution prepared as recommended has been 
demonstrated in non-PVC bags up to 48 hours when stored between 2 to 8°C.  
 
Docetaxel infusion solution is supersaturated, therefore may cristallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded.  
 
 Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
you no longer use. These measures will help protect the environment. 
 
6. Contents of the pack and other information 
 
What Docetaxel Zentiva contains 
- The active substance is docetaxel (as trihydrate). Each ml of concentrate for solution for infusion 
contains 20 mg docetaxel.  
- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and citric acid. 
 
What Docetaxel Zentiva looks like and contents of the pack 
Docetaxel Zentiva concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a 15 ml clear colourless glass vial with a blue aluminium seal and a blue 
plastic flip-off cap. 
 
Each box contains one vial of 8 ml concentrate (160 mg docetaxel). 
 
Marketing Authorisation Holder 
 
Zentiva k.s.  
U kabelovny 130  
102 37 Prague 10  
Czech Republic 
 
Manufacturer(s) 
Sanofi-Aventis Deutschland GmbH 
Industriepark Höchst 



182 

65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
België/Belgique/Belgien 
Zentiva, k.s. 
Tél/Tel: +32 280 86 420 
PV-Belgium@zentiva.com 
 

Lietuva 
Zentiva, k.s. 
Tel: +370 52152025 
PV-Lithuania@zentiva.com 

България 
Zentiva, k.s. 
Тел: + 359 2 805 72 08 
PV-Bulgaria@zentiva.com 
 

Luxembourg/Luxemburg 
Zentiva, k.s. 
Tél/Tel: +352 208 82330 
PV-Luxembourg@zentiva.com 

Česká republika 
Zentiva, k.s. 
Tel: +420 267 241 111 
PV-Czech-Republic@zentiva.com 

Magyarország 
Zentiva, k.s. 
Tel.: +36 165 55 722 
PV-Hungary@zentiva.com 

Danmark 
Zentiva, k.s. 
Tlf: +45 787 68 400 
PV-Denmark@zentiva.com 
 

Malta 
Zentiva, k.s. 
Tel: +356 277 82 052 
PV-Malta@zentiva.com 

Deutschland 
Zentiva Pharma GmbH  
Tel: +49 (0) 800 53 53 010 
PV-Germany@zentiva.com 
 

Nederland 
Zentiva, k.s. 
Tel: +31 202 253 638 
PV-Netherlands@zentiva.com 

Eesti 
Zentiva, k.s. 
Tel: +372 52 70308 
PV-Estonia@zentiva.com 
 

Norge 
Zentiva, k.s. 
Tlf: +47 219 66 203 
PV-Norway@zentiva.com 

Ελλάδα 
Zentiva, k.s. 
Τηλ: +30 211 198 7510 
PV-Greece@zentiva.com 
 

Österreich 
Zentiva, k.s. 
Tel: +43 720 778 877 
PV-Austria@zentiva.com 

España 
Zentiva, k.s. 
Tel: +34 931 815 250 
PV-Spain@zentiva.com 
 

Polska 
Zentiva Polska Sp. z o.o. 
Tel: + 48 22 375 92 00 
PV-Poland@zentiva.com 

France 
Zentiva France 
Tél: +33 (0) 800 089 219  
PV-France@zentiva.com 
 

Portugal 
Zentiva Portugal, Lda 
Tel: +351210601360 
PV-Portugal@zentiva.com 

Hrvatska 
Zentiva, k.s. 

România 
S.C. ZENTIVA S.A.



183 

Tel: +385 155 17 772 
PV-Croatia@zentiva.com 
 
Ireland 
Zentiva, k.s. 
Tel: +353 766 803 944 
PV-Ireland@zentiva.com 
 

Tel: +40 021 304 7597 
PV-Romania@zentiva.com 
 
Slovenija 
Zentiva, k.s. 
Tel: +386 360 00 408 
PV-Slovenia@zentiva.com 

Ísland 
Zentiva, k.s. 
Sími: +354 539 0650 
PV-Iceland@zentiva.com 
 

Slovenská republika 
Zentiva, a.s. 
Tel: +421 2 3918 3010 
PV-Slovakia@zentiva.com 

Italia 
Zentiva Italia S.r.l. 
 +39-02-38598801 
PV-Italy@zentiva.com 

Suomi/Finland 
Zentiva, k.s. 
Puh/Tel: +358 942 598 648 
PV-Finland@zentiva.com 

Κύπρος 
Zentiva, k.s. 
Τηλ: +357 240 30 144 
PV-Cyprus@zentiva.com 
 

Sverige 
Zentiva, k.s. 
Tel: +46 840 838 822 
PV-Sweden@zentiva.com 

Latvija 
Zentiva, k.s. 
Tel: +371 67893939 
PV-Latvia@zentiva.com 

United Kingdom 
Zentiva Pharma UK Limited 
Tel: +44 (0) 845 372 7101 
PV-United-Kingdom@zentiva.com 

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



184 

The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL ZENTIVA 160 mg/8 ml 
CONCENTRATE FOR SOLUTION FOR INFUSION 
 
 
It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 
Zentiva infusion solution. 
 
Recommendations for the safe handling 
Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing its solutions. The use of gloves is recommended.  
 
If Docetaxel Zentiva concentrate or infusion solution should come into contact with skin, wash 
immediately and thoroughly with soap and water. If it should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation of the intravenous administration 
 
Preparation of the infusion solution 
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Docetaxel Zentiva 160 mg/8 ml concentrate for solution for 
infusion, which contains only 1 vial). 
 
Docetaxel Zentiva 160 mg/8 ml concentrate for solution for infusion requires NO prior dilution 
with a solvent and is ready to add to the infusion solution.  
 Each vial is for single use and should be used immediately after opening. If not used 

immediately, in-use storage times and conditions are the responsibility of the user. More than 
one vial of concentrate for solution for infusion may be necessary to obtain the required dose for 
the patient. For example, a dose of 140 mg docetaxel would require 7 ml docetaxel concentrate 
for solution. 

 Aseptically withdraw the required amount of concentrate for solution for infusion with a 
calibrated syringe fitted with a 21G needle. 

In Docetaxel Zentiva 160 mg/8 ml vial the concentration of docetaxel is 20 mg/ml. 
 Then, inject via a single injection (one shot) into a 250 ml infusion bag or bottle containing 

either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose 
greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that 
a concentration of 0.74 mg/ml docetaxel is not exceeded. 

 Mix the infusion bag or bottle manually using a rocking motion. 
 From a microbiological point of view, reconstitution /dilution must take place in controlled and 

aseptic conditions and the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user. 
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored 
below 25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour 
infusion intravenous administration).  
In addition, physical and chemical in-use stability of the infusion solution prepared as 
recommended has been demonstrated in non-PVC bags up to 48 hours when stored between 
2°C to 8°C.  
Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals 
appear, the solution must no longer be used and shall be discarded. 

 As with all parenteral products, infusion solution should be visually inspected prior to use, 
solutions containing a precipitate should be discarded. 

 
Disposal 
All materials that have been utilised for dilution and administration should be disposed of according to 
standard procedures. Do not throw away any medicines via wastewater. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.  


	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET