Docetaxel Mylan
1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 20 mg/1 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate for solution for infusion contains 20 mg of docetaxel (anhydrous). 
One vial of 1 ml of concentrate contains 20 mg of docetaxel. 
 
Excipient with known effect: 
 
Each ml of concentrate for solution for infusion contains 395 mg of ethanol anhydrous. 
 
One vial of 1 ml of concentrate contains 395 mg of ethanol anhydrous. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is pale yellow to brownish-yellow.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan is indicated for the treatment of patients with locally advanced or metastatic non-
small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Mylan 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 Mylan in combination with prednisone or prednisolone is indicated for the treatment of 
patients with hormone refractory metastatic prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Mylan 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 Mylan 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). 
 
Recommended dose 
 
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). Prophylactic G-CSF 
may be used to mitigate the risk of haematological toxicities. 
For 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). 
 
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). 
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. 

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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 

The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
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 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 

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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 a 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%. 

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. 
 

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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 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 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). 
 
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. 
 
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). 

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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). 
 
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. 
 
Cutaneous reactions 
 
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). 
 
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 

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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). 
 
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. 
 
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). 
 
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). 
 

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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). 
 

Leukaemia 

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 
 

Patients with 4+ nodes 

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 demonstrated at the final analysis (see section 5.1). 
 

Older people 

There are limited available data in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 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. 
 
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 (alcohol), i.e. up to 0.395 g per vial, equivalent to 
10 ml of beer or 4 ml wine per vial. 
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. 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
The amount of alcohol in this medicinal product may impair the patients ability to drive or use 
machines. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 . 

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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. 
 
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. 
 

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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. 
 
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 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). 

 
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. 
 
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). 
 
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. 

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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 list of adverse reactions in breast cancer for Docetaxel 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%)   

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon 
adverse 
reactions 

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%) 

 

 
Description of selected adverse reactions in breast cancer for Docetaxel 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. 
 

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Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

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MedDRA system 
organ classes 

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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 
 

 

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

 

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MedDRA system organ 
classes 
 

Very common adverse 
reactions 

Common adverse reactions  

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 100 mg/m² in combination 
with trastuzumab 
 
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. 
 
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). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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%) 

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MedDRA system organ 
Classes 

Very common adverse 
reactions 
 

Common adverse reactions 
 

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%) 

 
Tabulated list of adverse reactions in prostate cancer for Docetaxel 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%) 

 

 

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Tabulated list of adverse reactions in breast cancer for adjuvant therapy with docetaxel 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%) 

  

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%) 

  

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MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Investigations 
 

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

 

 
Description of selected adverse reactions for adjuvant therapy with Docetaxel 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 

Peripheral sensory neuropathy was observed to be ongoing during follow-up in 10 patients out of the 
84 patients with peripheral sensory neuropathy at the end of the chemotherapy in the node positive 
breast cancer study (TAX316). 
 
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. One patient in TAC arm died because of dilated 
cardiomyopathy. 
 
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 and 645 of 736 FAC patients.   
At the end of the follow-up period (actual median follow-up time of 96 months), alopecia was 
observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study, alopecia persisted into the follow-up period (median follow-up time of 10 
years and 5 months) and 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. 
 
Reproductive system and breast disorders 

Amenorrhoea was observed to be ongoing during follow-up in 121 patients out of the 202 patients 
with amenorrhoea at the end of the chemotherapy in study TAX316. 
In GEICAM 9805 study, amenorrhoea persisted into the follow-up period (median follow-up time of 
10 years and 5 months) and was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 
patients (1.0 %) in FAC arm. 
 
General disorders and administration site conditions 

In study TAX316, peripheral oedema was observed to be ongoing in 19 patients out of the 
119 patients with peripheral oedema in the TAC arm and 4 patients out of the 23 patients with 
peripheral oedema in the FAC arm. 
In study GEICAM 9805, lymphoedema was observed to be ongoing in 4 of the 5 patients in TAC arm 
and in 1 of the 2 patients in FAC arm at the end of the chemotherapy, and did not resolve during the 
follow-up period (median follow-up time of 10 years and 5 months). Asthenia persisted into the 
follow-up period (median follow-up time of 10 years and 5 months) and was observed to be ongoing 
in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. 
 

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Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 4 of 744 TAC patients 
and in 1 of 736 FAC patients. Myelodysplastic syndrome was reported in 2 of 744 TAC patients and 
in 1 of 736 FAC patients. 
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 (%) 

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 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%) 

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MedDRA system organ classes Very common adverse 
reactions 

Common adverse reactions 
 

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 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 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%) 

  

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MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 

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   
 
 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 

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MedDRA system 
organ classes 

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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 
 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association 
with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy 
 
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. 
 
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. 
 

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Cardiac disorders 

Rare cases of myocardial infarction have been reported. 
 
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 occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal 
perforation, colitis ischaemic, colitis and neutropenic enterocolitis have been reported. 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 

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some 
cases concomitant factors may have contributed to the development of these effects. Sclerodermal-like 
changes usually preceded by peripheral lymphoedema have been reported with docetaxel. Cases of 
persisting alopecia 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 concomitant nephrotoxic medicinal products and gastro-intestinal 
disorders. 
 
General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 
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 hyponatraemia have been reported, mostly associated with dehydration, vomiting and 
pneumonia. 
 
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. 
 
 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, 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 in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 
 

Data from a multicenter open label randomized 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 randomized 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 cyclosphosphamide 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 estrogen 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 
enrollment 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 

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(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 
analyzed: 
 
  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 nodenegative breast cancer eligible to receive chemotherapy (GEICAM 9805) 
 
Data from a multicenter open label randomized trial support the use of docetaxel for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 
1060 patients were randomized to receive either docetaxel 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 cyclosphosphamide 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 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 randomized. 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), 

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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 
timepoint, and 91.3 % in the TAC arm and 89% in the FAC arm, at the 10-year follow-up timepoint. 
 
The positive benefit risk ratio for TAC compared to FAC remained unchanged. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analyzed in the primary analysis (at the median follow-up time of 77 months) (see table below): 
 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 
(Intent-to-Treat Analysis) 
 

Patient subset 
 

Number of patients 
in TAC group 

Disease Free Survival 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1 
<50 years 
≥50 years 

 
260 
279 

 
0.67 
0.67 

 
0.43-1.05 
0.43-1.05 

Age category 2 
<35 years 
≥35 years 

 
42 

497 

 
0.31 
0.73 

 
0.11-0.89 
0.52-1.01 

Hormonal receptor 
status 
Negative 
Positive 

 
 

195 
344 

 
 

0.7 
0.62 

 
 

0.45-1.1 
0.4-0.97 

Tumour size 
≤2 cm 
>2 cm 

 
285 
254 

 
0.69 
0.68 

 
0.43-1.1 

0.45-1.04 
Histological grade 
Grade1 (includes grade 
not assessed) 
Grade 2 
Grade 3 

 
64 

 
216 
259 

 
0.79 

 
0.77 
0.59 

 
0.24-2.6 

 
0.46-1.3 
0.39-0.9 

Menopausal status 
Pre-Menopausal 
Post-Menopausal 

 
285 
254 

 
0.64 
0.72 

 
0.40-1 

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. 
 

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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 = estrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumor size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 
Docetaxel 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, multicenter, randomized 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 randomized 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%). 
 

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Docetaxel in combination with doxorubicin 

 
One large randomized 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. 
 
Docetaxel 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 randomized 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 in combination with capecitabine 

 

Data from one multicenter, 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 

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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. 
 
Docetaxel 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, 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. 
 

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Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnosfky 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 

 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
hormone refractory metastatic prostate cancer were evaluated in a randomized multicenter phase III 
study. A total of 1006 patients with KPS ≥ 60 were randomized 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: 
 
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 
Tumor 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. 
 
Gastric adenocarcinoma 

 
A multicenter, open-label, randomized 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 

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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 logrank 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, multicenter, open-label, 
randomized study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO performance status 0 or 1, were randomized 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). 

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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 
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) 
**Logrank 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). 
 

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Clinical benefit parameters 

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 randomized, multicenter 
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 randomized 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 anytime 
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: 
 
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 

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Endpoint Docetaxel + Cis + 5-FU 
n = 255 

Cis  +  5-FU 
n = 246 

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 
 
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 α, β and γ 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. 
 
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).  
 

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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. 
 
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 
 
Ethanol anhydrous 
Polysorbate 80 
Citric acid (pH adjustment) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 

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6.3 Shelf life 
 
Unopened vial 
12 months. 
 
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, 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 non-PVC 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. 
 
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 after dilution of the diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
6 ml clear glass Type I vial with a bromobutyl rubber stopper and aluminium seal and a plastic flip-off 
cap containing 1 ml of concentrate for solution for infusion. 
 
Box of 1 vial, or 5 vials. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Mylan is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Mylan solutions. The use of gloves is 
recommended. 
 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with skin, wash 
immediately and thoroughly with soap and water. 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 

 
More than one vial may be necessary to obtain the required dose for the patient. 

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Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
volume of concentrate for solution containing 20 mg/ml docetaxel from the appropriate number of 
vials using graduated syringes fitted with a 21G needle. For example, a dose of 140 mg docetaxel 
would require 7 ml docetaxel concentrate for solution for infusion. 
 
Inject the required volume of concentrate for solution 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 and normal lighting conditions 
including the one hour infusion to the patient. 
 
As with all parenteral products, Docetaxel Mylan concentrate for solution or diluted solution for 
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 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/001 - 1 vial 
EU/1/11/748/002 - 5 vials 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 January 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 

 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 80 mg/4 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate for solution for infusion contains 20 mg of docetaxel (anhydrous). 
One vial of 4 ml of concentrate contains 80 mg of docetaxel. 
 
Excipient with known effect: 
 
Each ml of concentrate for solution for infusion contains 395 mg of ethanol anhydrous. 
 
One vial of 4 ml of concentrate contains 1.58 g of ethanol anhydrous.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is pale yellow to brownish-yellow.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan is indicated for the treatment of patients with locally advanced or metastatic non-
small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Mylan 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 Mylan in combination with prednisone or prednisolone is indicated for the treatment of 
patients with hormone refractory metastatic prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Mylan 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 Mylan 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). 
 
Recommended dose 
 
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). Prophylactic G-CSF 
may be used to mitigate the risk of haematological toxicities. 
For 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). 
 
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). 
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. 

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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 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 

The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
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 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 

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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 a 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%. 

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. 
 

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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 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 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). 
 
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. 
 
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). 

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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). 
 
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. 
 
Cutaneous reactions 
 
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). 
 
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 

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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). 
 
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. 
 
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). 
 
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). 
 

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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). 
 

Leukaemia 

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 
 

Patients with 4+ nodes 

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 demonstrated at the final analysis (see section 5.1). 
 

Older people 

There are limited available data in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 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. 
 
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 (alcohol), i.e. up to 1.58 g per vial, equivalent to 
40 ml of beer or 17 ml wine per vial. 
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. 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
The amount of alcohol in this medicinal product may impair the patients ability to drive or use 
machines. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 . 

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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. 
 
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. 
  

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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. 
 
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 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). 

 
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. 
 
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). 
 
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. 

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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 list of adverse reactions in breast cancer for Docetaxel 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%)   

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon 
adverse 
reactions 

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%) 

 

 
Description of selected adverse reactions in breast cancer for Docetaxel 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. 
 

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Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

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MedDRA system 
organ classes 

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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 
 

 

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

 

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MedDRA system organ 
classes 
 

Very common adverse 
reactions 

Common adverse reactions  

General disorders 
andadministration 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 100 mg/m² in combination 
with trastuzumab 
 
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. 
 
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). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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%) 

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MedDRA system organ 
classes 

Very common adverse 
reactions 
 

Common adverse reactions 
 

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%) 

 
Tabulated list of adverse reactions in prostate cancer for Docetaxel 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%) 

 

 

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Tabulated list of adverse reactions in breast cancer for adjuvant therapy with docetaxel 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%) 

  

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%) 

  

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MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Investigations 
 

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

 

 
Description of selected adverse reactions for adjuvant therapy with Docetaxel 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 

Peripheral sensory neuropathy was observed to be ongoing during follow-up in 10 patients out of the 
84 patients with peripheral sensory neuropathy at the end of the chemotherapy in the node positive 
breast cancer study (TAX316). 
 
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. One patient in TAC arm died because of dilated 
cardiomyopathy. 
 
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 and 645 of 736 FAC patients.  
At the end of the follow-up period (actual median follow-up time of 96 months), alopecia was 
observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study, alopecia persisted into the follow-up period (median follow-up time of 10 
years and 5 months) and 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. 
 
Reproductive system and breast disorders 

Amenorrhoea was observed to be ongoing during follow-up in 121 patients out of the 202 patients 
with amenorrhoea at the end of the chemotherapy in study TAX316. 
In GEICAM 9805 study, amenorrhoea persisted into the follow-up period (median follow-up time of 
10 years and 5 months) and was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 
patients (1.0 %) in FAC arm. 
 
General disorders and administration site conditions 

In study TAX316, peripheral oedema was observed to be ongoing in 19 patients out of the 
119 patients with peripheral oedema in the TAC arm and 4 patients out of the 23 patients with 
peripheral oedema in the FAC arm. 
In study GEICAM 9805, lymphoedema was observed to be ongoing in 4 of the 5 patients in TAC arm 
and in 1 of the 2 patients in FAC arm at the end of the chemotherapy, and did not resolve during the 
follow-up period (median follow-up time of 10 years and 5 months). Asthenia persisted into the 
follow-up period (median follow-up time of 10 years and 5 months) and was observed to be ongoing 
in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. 
 

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Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 4 of 744 TAC patients 
and in 1 of 736 FAC patients. Myelodysplastic syndrome was reported in 2 of 744 TAC patients and 
in 1 of 736 FAC patients.  
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 (%) 

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 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%) 

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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 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 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%) 

  

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MedDRA system 
organ classes 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 

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   
 
 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 

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MedDRA system 
organ classes 

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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 
 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 

Cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association 
with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy 
 
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. 
 
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. 
 

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Cardiac disorders 

Rare cases of myocardial infarction have been reported. 
 
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 occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal 
perforation, colitis ischaemic, colitis and neutropenic enterocolitis have been reported. 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 

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some 
cases concomitant factors may have contributed to the development of these effects. Sclerodermal-like 
changes usually preceded by peripheral lymphoedema have been reported with docetaxel. Cases of 
persisting alopecia 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 concomitant nephrotoxic medicinal products and gastro-intestinal 
disorders. 
 
General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 
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 hyponatraemia have been reported, mostly associated with dehydration, vomiting and 
pneumonia. 
 
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. 
 
 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, 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 in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 
 

Data from a multicenter open label randomized 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 randomized 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 cyclosphosphamide 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 estrogen 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 
enrollment 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 

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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 
analyzed: 
 
  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 nodenegative breast cancer eligible to receive chemotherapy (GEICAM 9805) 
 
Data from a multicenter open label randomized trial support the use of docetaxel for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 
1060 patients were randomized to receive either docetaxel 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 cyclosphosphamide 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 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 randomized. 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), 

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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 
timepoint, and 91.3 % in the TAC arm and 89% in the FAC arm, at the 10-year follow-up timepoint. 
 
The positive benefit risk ratio for TAC compared to FAC remained unchanged. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analyzed in the primary analysis (at the median follow-up time of 77 months) (see table below): 
 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 
(Intent-to-Treat Analysis) 
 

Patient subset 
 

Number of patients 
in TAC group 

Disease Free Survival 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1 
<50 years 
≥50 years 

 
260 
279 

 
0.67 
0.67 

 
0.43-1.05 
0.43-1.05 

Age category 2 
<35 years 
≥35 years 

 
42 

497 

 
0.31 
0.73 

 
0.11-0.89 
0.52-1.01 

Hormonal receptor 
status 
Negative 
Positive 

 
 

195 
344 

 
 

0.7 
0.62 

 
 

0.45-1.1 
0.4-0.97 

Tumour size 
≤2 cm 
>2 cm 

 
285 
254 

 
0.69 
0.68 

 
0.43-1.1 

0.45-1.04 
Histological grade 
Grade1 (includes grade 
not assessed) 
Grade 2 
Grade 3 

 
64 

 
216 
259 

 
0.79 

 
0.77 
0.59 

 
0.24-2.6 

 
0.46-1.3 
0.39-0.9 

Menopausal status 
Pre-Menopausal 
Post-Menopausal 

 
285 
254 

 
0.64 
0.72 

 
0.40-1 

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. 
 

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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 = estrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumor size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 
Docetaxel 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, multicenter, randomized 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 randomized 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%). 
 

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Docetaxel in combination with doxorubicin 

 
One large randomized 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. 
 
Docetaxel 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 randomized 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 in combination with capecitabine 

 

Data from one multicenter, 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 

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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. 
 
Docetaxel 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, 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. 
 

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Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnosfky 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 

 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
hormone refractory metastatic prostate cancer were evaluated in a randomized multicenter phase III 
study. A total of 1006 patients with KPS ≥ 60 were randomized 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: 
 
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 
Tumor 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. 
 
Gastric adenocarcinoma 

 
A multicenter, open-label, randomized 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 

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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 logrank 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, multicenter, open-label, 
randomized study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO performance status 0 or 1, were randomized 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). 

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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 
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) 
**Logrank 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). 
 

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Clinical benefit parameters 

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 randomized, multicenter 
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 randomized 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 anytime 
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: 
 
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 

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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 
 
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 α, β and γ 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. 
 
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).  
 

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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. 
 
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 
 
Ethanol anhydrous 
Polysorbate 80 
Citric acid (pH adjustment) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 

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6.3 Shelf life 
 
Unopened vial 
12 months. 
 
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, 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 non-PVC 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. 
 
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 after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
10 ml clear glass Type I vial with a bromobutyl rubber stopper and aluminium seal and a plastic flip-
off cap containing 4 ml of concentrate for solution for infusion. 
 
Box of 1 vial, or 5 vials. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Mylan is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Mylan solutions. The use of gloves is 
recommended. 
 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with skin, wash 
immediately and thoroughly with soap and water. 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 

 
More than one vial may be necessary to obtain the required dose for the patient. 

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Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
volume of concentrate for solution containing 20 mg/ml docetaxel from the appropriate number of 
vials using graduated syringes fitted with a 21G needle. For example, a dose of 140 mg docetaxel 
would require 7 ml docetaxel concentrate for solution for infusion. 
 
Inject the required volume of concentrate for solution 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 and normal lighting conditions 
including the one hour infusion to the patient. 
 
As with all parenteral products, Docetaxel Mylan concentrate for solution or diluted solution for 
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 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/003 - 1 vial 
EU/1/11/748/004 - 5 vials 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 January 2012 
 

 
10. DATE OF REVISION OF THE TEXT 
 
 

 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 200 mg/10 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate for solution for infusion contains 20 mg of docetaxel (anhydrous). 

One vial of 10 ml of concentrate contains 200 mg of docetaxel. 
 
Excipient with known effect: 
 
Each ml of concentrate for solution for infusion contains 395 mg of ethanol anhydrous. 
 
One vial of 10 ml of concentrate contains 3,95 g of ethanol anhydrous. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is pale yellow to brownish-yellow.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan is indicated for the treatment of patients with locally advanced or metastatic non-
small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Mylan 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 Mylan in combination with prednisone or prednisolone is indicated for the treatment of 
patients with hormone refractory metastatic prostate cancer. 
 
Gastric adenocarcinoma 
 
Docetaxel Mylan 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 Mylan 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). 
 
Recommended dose 
 
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). Prophylactic G-CSF 
may be used to mitigate the risk of haematological toxicities. 
For 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). 
 
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). 
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 

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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 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 

The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily 
is administered continuously (see section 5.1). 
 
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 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 

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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 a 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%. 

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. 
 

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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 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 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). 
 
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. 
 
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). 

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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). 
 
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. 
 
Cutaneous reactions 
 
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). 
 
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 

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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). 
 
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. 
 
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). 
 
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). 
 

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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). 
 

Leukaemia 

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 
 

Patients with 4+ nodes 

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 demonstrated at the final analysis (see section 5.1). 
 

Older people 

There are limited available data in patients > 70 years of age on docetaxel use in combination with 
doxorubicin and cyclophosphamide. 
 
Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 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. 
 
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 (alcohol), i.e. up to 3.95 g per vial, equivalent to 
100 ml of beer or 40 ml wine per vial. 
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. 
 
The amount of alcohol in this medicinal product may alter the effects of other medicinal products. 
 
The amount of alcohol in this medicinal product may impair the patients ability to drive or use 
machines. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 . 

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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. 
 
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. 
 

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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. 
 
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 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). 

 
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. 
 
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). 
 
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. 

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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 list of adverse reactions in breast cancer for Docetaxel 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%)   

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon 
adverse 
reactions 

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%) 

 

 
Description of selected adverse reactions in breast cancer for Docetaxel 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. 
 

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Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

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MedDRA system 
organ classes 

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in non-small cell lung cancer for Docetaxel 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 
 

 

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MedDRA system 
organ classes 

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

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%) 

 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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 

 

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MedDRA system organ 
classes 
 

Very common adverse 
reactions 

Common adverse reactions  

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 100 mg/m² in combination 
with trastuzumab 
 
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. 
 
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). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 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%) 

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MedDRA system organ 
classes 

Very common adverse 
reactions 
 

Common adverse reactions 
 

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%) 

 
Tabulated list of adverse reactions in prostate cancer for Docetaxel 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%) 

 

 

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Tabulated list of adverse reactions in breast cancer for adjuvant therapy with docetaxel 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%) 

  

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%) 

  

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MedDRA system 
organ classes 
 

Very common adverse 
reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Investigations 
 

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

 

 
Description of selected adverse reactions for adjuvant therapy with Docetaxel 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 

Peripheral sensory neuropathy was observed to be ongoing during follow-up in 10 patients out of the 
84 patients with peripheral sensory neuropathy at the end of the chemotherapy in the node positive 
breast cancer study (TAX316). 
 
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. One patient in TAC arm died because of dilated 
cardiomyopathy. 
 
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 and 645 of 736 FAC patients.  
At the end of the follow-up period (actual median follow-up time of 96 months), alopecia was 
observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). 
In GEICAM 9805 study, alopecia persisted into the follow-up period (median follow-up time of 10 
years and 5 months) and 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. 
 
Reproductive system and breast disorders 

Amenorrhoea was observed to be ongoing during follow-up in 121 patients out of the 202 patients 
with amenorrhoea at the end of the chemotherapy in study TAX316. 
In GEICAM 9805 study, amenorrhoea persisted into the follow-up period (median follow-up time of 
10 years and 5 months) and was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 
patients (1.0 %) in FAC arm. 
 
General disorders and administration site conditions 

In study TAX316, peripheral oedema was observed to be ongoing in 19 patients out of the 
119 patients with peripheral oedema in the TAC arm and 4 patients out of the 23 patients with 
peripheral oedema in the FAC arm. 
In study GEICAM 9805, lymphoedema was observed to be ongoing in 4 of the 5 patients in TAC arm 
and in 1 of the 2 patients in FAC arm at the end of the chemotherapy, and did not resolve during the 
follow-up period (median follow-up time of 10 years and 5 months). Asthenia persisted into the 
follow-up period (median follow-up time of 10 years and 5 months) and was observed to be ongoing 
in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. 
 
Acute leukaemia / Myelodysplastic syndrome 

After 10 years of follow up in study TAX316, acute leukaemia was reported in 4 of 744 TAC patients 
and in 1 of 736 FAC patients. Myelodysplastic syndrome was reported in 2 of 744 TAC patients and 
in 1 of 736 FAC patients. 

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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 (%) 

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 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%) 

 

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Description of selected adverse reactions in gastric adenocarcinoma cancer for Docetaxel 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 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%)  

  

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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 

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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) 

Cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association 
with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy 
 
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. 
 
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. 

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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 occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal 
perforation, colitis ischaemic, colitis and neutropenic enterocolitis have been reported. 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 

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, 
Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported with docetaxel. In some 
cases concomitant factors may have contributed to the development of these effects. Sclerodermal-like 
changes usually preceded by peripheral lymphoedema have been reported with docetaxel. Cases of 
persisting alopecia 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 concomitant nephrotoxic medicinal products and gastro-intestinal 
disorders. 
 
General disorders and administration site conditions 

Radiation recall phenomena have rarely been reported. 
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 hyponatraemia have been reported, mostly associated with dehydration, vomiting and 
pneumonia. 
 
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. 
 
 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, 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 in combination with doxorubicin and cyclophosphamide: adjuvant therapy 

 

Patients with operable node-positive breast cancer (TAX 316) 
 

Data from a multicenter open label randomized 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 randomized 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 cyclosphosphamide 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 estrogen 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 
enrollment 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 

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(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 
analyzed: 
 
  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 nodenegative breast cancer eligible to receive chemotherapy (GEICAM 9805) 
 
Data from a multicenter open label randomized trial support the use of docetaxel for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 
1060 patients were randomized to receive either docetaxel 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 cyclosphosphamide 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 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 randomized. 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. 

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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 
timepoint, and 91.3 % in the TAC arm and 89% in the FAC arm, at the 10-year follow-up timepoint. 
 
The positive benefit risk ratio for TAC compared to FAC remained unchanged. 
 
TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analyzed in the primary analysis (at the median follow-up time of 77 months) (see table below): 
 
Subset Analyses-Adjuvant Therapy in Patients with Node-negative Breast Cancer Study 
(Intent-to-Treat Analysis) 
 

Patient subset 
 

Number of patients 
in TAC group 

Disease Free Survival 
Hazard ratio* 95% CI 

Overall 539 0.68 0.49-0.93 
Age category 1 
<50 years 
≥50 years 

 
260 
279 

 
0.67 
0.67 

 
0.43-1.05 
0.43-1.05 

Age category 2 
<35 years 
≥35 years 

 
42 

497 

 
0.31 
0.73 

 
0.11-0.89 
0.52-1.01 

Hormonal receptor 
status 
Negative 
Positive 

 
 

195 
344 

 
 

0.7 
0.62 

 
 

0.45-1.1 
0.4-0.97 

Tumour size 
≤2 cm 
>2 cm 

 
285 
254 

 
0.69 
0.68 

 
0.43-1.1 

0.45-1.04 
Histological grade 
Grade1 (includes grade 
not assessed) 
Grade 2 
Grade 3 

 
64 

 
216 
259 

 
0.79 

 
0.77 
0.59 

 
0.24-2.6 

 
0.46-1.3 
0.39-0.9 

Menopausal status 
Pre-Menopausal 
Post-Menopausal 

 
285 
254 

 
0.64 
0.72 

 
0.40-1 

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. 
 

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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 = estrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumor size >5 cm 
 
The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 
 
Docetaxel 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, multicenter, randomized 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 randomized 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%). 
 

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Docetaxel in combination with doxorubicin 

 
One large randomized 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. 
 
Docetaxel 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 randomized 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 in combination with capecitabine 

 

Data from one multicenter, 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 

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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. 
 
Docetaxel 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, 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. 
 

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Secondary end-points included change of pain, global rating of quality of life by EuroQoL-5D, Lung 
Cancer Symptom Scale, and changes in Karnosfky 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 

 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in patients with 
hormone refractory metastatic prostate cancer were evaluated in a randomized multicenter phase III 
study. A total of 1006 patients with KPS ≥ 60 were randomized 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: 
 
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 
Tumor 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. 
 
Gastric adenocarcinoma 

 
A multicenter, open-label, randomized 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 

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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 logrank 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, multicenter, open-label, 
randomized study (TAX323). In this study, 358 patients with inoperable locally advanced SCCHN, 
and WHO performance status 0 or 1, were randomized 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). 

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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 
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) 
**Logrank 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). 
 

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Clinical benefit parameters 

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 randomized, multicenter 
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 randomized 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 anytime 
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: 
 
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 

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Endpoint Docetaxel + Cis + 5-FU 
n = 255 

Cis  +  5-FU 
n = 246 

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 
 
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 α, β and γ 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. 
 
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).  
 

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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. 
 
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 
 
Ethanol anhydrous 
Polysorbate 80 
Citric acid (pH adjustment) 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 

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6.3 Shelf life 
 
Unopened vial 
12 months. 
 
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, 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 non-PVC 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. 
 
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 after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
15 ml clear glass Type I vial with a bromobutyl rubber stopper and aluminium seal and a plastic flip-
off cap containing 10 ml of concentrate for solution for infusion. 
 
Box of 1 vial, or 5 vials. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Mylan is an antineoplastic agent and, as with other potentially toxic compounds, caution 
should be exercised when handling it and preparing Docetaxel Mylan solutions. The use of gloves is 
recommended. 
 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with skin, wash 
immediately and thoroughly with soap and water. 
If Docetaxel Mylan concentrate or solution for infusion should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 
 
Preparation for the intravenous administration 
 
Preparation of the infusion solution 

 
More than one vial may be necessary to obtain the required dose for the patient. 

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Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
volume of concentrate for solution containing 20 mg/ml docetaxel from the appropriate number of 
vials using graduated syringes fitted with a 21G needle. For example, a dose of 140 mg docetaxel 
would require 7 ml docetaxel concentrate for solution for infusion. 
 
Inject the required volume of concentrate for solution 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 and normal lighting conditions 
including the one hour infusion to the patient. 
 
As with all parenteral products, Docetaxel Mylan concentrate for solution or diluted solution for 
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 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/005 - 1 vial 
EU/1/11/748/006 - 5 vials 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 January 2012 
 

 
10. DATE OF REVISION OF THE TEXT 
 
 

 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 

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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 

 
 
 

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
 

Name and address of the manufacturer responsible for batch release 
 

Mylan S.A.S. 
117 allée des Parcs 
F-69 800 Saint Priest 
France 
 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

 

 Periodic Safety Update Reports  
 
The marketing authorisation holder shall submit periodic safety update reports 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) 
 
Not applicable 
 
 Obligation to conduct post-authorisation measures 
 
Not applicable 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 20 mg/1 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel (anhydrous). 
One vial of 1 ml of concentrate contains 20 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 

Excipients: polysorbate 80, ethanol anhydrous and citric acid. See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial of 1 ml  
5 vials of 1 ml  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Ready to add to infusion solution. 
Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial and add it 
directly into the infusion solution.  
Single-use vial. 
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 
 
 
8. EXPIRY DATE 
 
EXP: 
Read the leaflet for the shelf life of the diluted medicine. 

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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 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/001 - 1 vial 
EU/1/11/748/002 - 5 vials  
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 

 

16. INFORMATION IN BRAILLE 
 

 

Justification for not including Braille accepted 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Mylan 20 mg/1 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 

 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 mg/1 ml 
 
 
6. OTHER 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 80 mg/4 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel (anhydrous). 
One vial of 4 ml of concentrate contains 80 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 

Excipients: polysorbate 80, ethanol anhydrous and citric acid. See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial of 4 ml 
5 vials of 4 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Ready to add to infusion solution. 
Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial and add it 
directly into the infusion solution.  
Single-use vial. 
Intravenous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF SIGHT AND THE REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
Read the leaflet for the shelf life of the diluted medicine. 
 

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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 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/003 - 1 vial 
EU/1/11/748/004 - 5 vials 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 

 

16. INFORMATION IN BRAILLE 
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Mylan 80 mg/4 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 

 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
80 mg/4 ml 
 
 
6. OTHER 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Mylan 200 mg/10 ml concentrate for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 20 mg docetaxel (anhydrous). 
One vial of 10 ml of concentrate contains 200 mg of docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 

Excipients: polysorbate 80, ethanol anhydrous and citric acid. See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial of 10 ml 
5 vials of 10 ml  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Ready to add to infusion solution. 
Withdraw the required amount of this docetaxel concentrate (20 mg/ml) from the vial and add it 
directly into the infusion solution.  
Single-use vial. 
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 
 
 
8. EXPIRY DATE 
 
EXP: 
Read the leaflet for the shelf life of the diluted medicine. 
 

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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 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 

Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/748/005 - 1 vial 
EU/1/11/748/006 - 5 vials  
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 

 

16. INFORMATION IN BRAILLE 
 

 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL / Docetaxel Mylan 200 mg/10 ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Mylan 200 mg/10 ml sterile concentrate 
docetaxel 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 

 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
200 mg/10 ml 
 
 
6. OTHER 
 
 

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B. PACKAGE LEAFLET 

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Package Leaflet: Information for the user 

 
Docetaxel Mylan 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 or hospital pharmacist. 
- 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 Mylan 20 mg/1 ml is and what it is used for 
2. What you need to know before you use Docetaxel Mylan 20 mg/1 ml 
3. How to use Docetaxel Mylan 20 mg/1 ml 
4. Possible side effects 
5. How to store Docetaxel Mylan 20 mg/1 ml 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Mylan 20 mg/1 ml is and what it is used for 
 
Docetaxel is a substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
Docetaxel Mylan 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 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 could be 
administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, docetaxel could be administered either alone or in combination with 
cisplatin. 
- For the treatment of prostate cancer, docetaxel is administered in combination with prednisone or 
prednisolone. 
- For the treatment of metastatic gastric cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
- For the treatment of head and neck cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Mylan 20 mg/1 ml 
 
You must not be given Docetaxel Mylan 
 
- if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Mylan 
- if the number of white blood cells is too low. 
- if you have a severe liver disease. 
 

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Warnings and precautions 
 
Before each treatment with Docetaxel Mylan, you will have blood tests to check that you have enough 
blood cells and sufficient liver function to receive Docetaxel Mylan. In case of white blood cells 
disturbances, you may experience associated fever or infections. 
 
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. 
 
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 Mylan 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 Mylan 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. 
Docetaxel Mylan contains alcohol. Discuss with your doctor if you suffer from alcohol dependency or 
liver impairment. See also section “Docetaxel Mylan contains ethanol” below. 
 
Other medicines and Docetaxel Mylan 
 
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 Mylan or 
the other medicine may not work as well as expected and you may be more likely to get a side effect. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Mylan must NOT be administered if you are pregnant unless clearly indicated by your 
doctor. 
 
You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy, because Docetaxel Mylan 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 Mylan. 
 
If you are a man being treated with Docetaxel Mylan 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 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
Docetaxel Mylan contains ethanol 
 
This medicine contains 50 vol % ethanol (alcohol), i.e. up to 0.395 g per vial equivalent to 10 ml of 
beer or 4 ml wine per vial. 
 
Harmful for those suffering from alcoholism. 
To be taken into account if you are pregnant or if you are 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 alter the effects of other medicines. 

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The amount of alcohol in this medicine may impair your ability to drive or use machines. 
 
 
3. How to use Docetaxel Mylan 20 mg/1 ml 
 
Docetaxel Mylan 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 Mylan 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 Mylan. 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. 
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 Mylan alone are: decrease in the number 
of red blood cells or white blood cells, hair loss, nausea, vomiting, sores in the mouth, diarrhoea and 
tiredness. 
 
The severity of adverse events of Docetaxel Mylan may be increased when Docetaxel Mylan is given 
in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions (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. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Mylan the following may occur, and the frequency may vary with the 
combinations of medicines that are received. 

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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) 
 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 
 tiredness; or flu-like symptoms 
 weight gain or loss. 
 
Common (may affect up to 1 in 10 people): 
 fungal infection of the mouth (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). 
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 inflammation of the colon, small intestine; intestinal perforation 
 blood clots. 
 
Frequency unknown: 
 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). 

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 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium in your blood. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Docetaxel Mylan 20 mg/1 ml 
 
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, dilution must take place in controlled and aseptic conditions. 
 
Use immediately the medicine once added into the non-PVC 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°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. 
 
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 Mylan 20 mg/1 ml contains  
 
The active substance is docetaxel. Each ml of concentrate for solution for infusion contains 20 mg 
docetaxel (anhydrous). 
One vial contains 20 mg of docetaxel. 
The other ingredients are polysorbate 80, ethanol anhydrous and citric acid.  
 
What Docetaxel Mylan 20 mg/1 ml looks like and contents of the pack 
 
Docetaxel Mylan concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a clear colourless glass vial with a rubber stopper and a plastic flip-off 
cap. 
Each vial contains 1 ml of concentrate. 
Each box contains 1 or 5 vials. 
 

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Marketing Authorisation Holder and Manufacturer 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00  
 

Lietuva 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

България 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00 (Belgium) 
 

Ceská republika 
MylanPharmaceuticals s.r.o. 
Tel: +420 274 770 201 
 

Magyarország 
Mylan Kft 
Tel: 36 1 8026993 

Danmark 
Mylan ApS  
Tlf: + 45 3694 4568  
 

Malta 
George Borg Barthet Ltd 
Tel: +356 21244205 
 

Deutschland 
Mylan dura GmbH  
Tel: + 49-(0) 6151 9512 0 
 

Nederland 
Mylan B.V 
Tel: + 31 (0)33 2997080 

Eesti 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Norge 
Mylan AB 
Tlf: + 46 8-555 227 50 (Sverige) 
 

Ελλάδα  
Generics Pharma Hellas ΕΠΕ  
Τηλ:  +30 210 9936410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 24 18 

España 
Mylan Pharmaceuticals, S.L 
tel: +  34 93 3786400 
 

Polska 
Mylan Sp.z.o.o 
Tel: +48 22 5466400 
 

France 
Mylan SAS 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Phone: + 00351 21 412 7200 
 

Hrvatska 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

România 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Ireland 
Mc Dermott Laboratories Ltd  
Tel: + 1800 272 272  
Allphar +353 1 4041600 
 

Slovenija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

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Ísland 
Mylan AB 
Tel: + 46 8-555 227 50 
 

Slovenská republika 
Mylan sr.o 
Tel: +421 2 32 604 901 
 

Italia 
Mylan S.p.A 
Tel: + +39/02-61246921 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: + 358 9-46 60 03  

Κύπρος 
Pharmaceutical Trading Co Ltd 
Τηλ: +35 7 24656165 
 

Sverige 
Mylan AB  
Tel: + 46 8-555 227 50 
 

Latvija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

United Kingdom 
Generics [UK] Ltd t/a Mylan 
Tel: +44 1707 853000 

 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL MYLAN CONCENTRATE FOR 
SOLUTION FOR INFUSION 
 

It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 

Mylan 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 Mylan 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 Mylan concentrate for solution for infusion, which 
contains only 1 vial). 
 
Docetaxel Mylan concentrate for solution for infusion requires NO prior dilution with a solvent 
and is ready to be added 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. 

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In Docetaxel Mylan, 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, 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. 
 

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Package Leaflet: Information for the user 

 
Docetaxel Mylan 80 mg/4 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 or hospital pharmacist. 
- 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 Mylan 80 mg/4 ml is and what it is used for 
2. What you need to know before you use Docetaxel Mylan 80 mg/4 ml 
3. How to use Docetaxel Mylan 80 mg/4 ml 
4. Possible side effects 
5. How to store Docetaxel Mylan 80 mg/4 ml 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Mylan 80 mg/4 ml is and what it is used for 
 
Docetaxel is a substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
Docetaxel Mylan 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 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 could be 
administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, docetaxel could be administered either alone or in combination with 
cisplatin. 
- For the treatment of prostate cancer, docetaxel is administered in combination with prednisone or 
prednisolone. 
- For the treatment of metastatic gastric cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
- For the treatment of head and neck cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Mylan 80 mg/4 ml 
 
You must not be given Docetaxel Mylan 
 
- if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Mylan 
- if the number of white blood cells is too low. 
- if you have a severe liver disease. 
 

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Warnings and precautions 
 
Before each treatment with Docetaxel Mylan, you will have blood tests to check that you have enough 
blood cells and sufficient liver function to receive Docetaxel Mylan. In case of white blood cells 
disturbances, you may experience associated fever or infections. 
 
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. 
 
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 Mylan 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 Mylan 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. 
Docetaxel Mylan contains alcohol. Discuss with your doctor if you suffer from alcohol dependency or 
liver impairment. See also section “Docetaxel Mylan contains ethanol” below. 
 
Other medicines and Docetaxel Mylan 
 
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 Mylan or 
the other medicine may not work as well as expected and you may be more likely to get a side effect. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Mylan must NOT be administered if you are pregnant unless clearly indicated by your 
doctor. 
 
You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy, because Docetaxel Mylan 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 Mylan. 
 
If you are a man being treated with Docetaxel Mylan 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 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
Docetaxel Mylan contains ethanol 
 
This medicine contains 50 vol % ethanol (alcohol), i.e. up to 1.58g per vial equivalent to 40 ml of beer 
or 17 ml wine per vial. 
 
Harmful for those suffering from alcoholism. 
To be taken into account if you are pregnant or if you are 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 alter the effects of other medicines. 

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The amount of alcohol in this medicine may impair your ability to drive or use machines. 
 
 
3. How to use Docetaxel Mylan 80 mg/4 ml 
 
Docetaxel Mylan 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 Mylan 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 Mylan. 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. 
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 Mylan alone are: decrease in the number 
of red blood cells or white blood cells, hair loss, nausea, vomiting, sores in the mouth, diarrhoea and 
tiredness. 
 
The severity of adverse events of Docetaxel Mylan may be increased when Docetaxel Mylan is given 
in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions (may affect more than 1 in 10 
people) may occur: 
 flushing, skin reactions, itching 
 chest tightness; difficulty in breathing 
 fever or chills 
 back pain 
 low blood pressure. 
More severe reactions may occur. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Mylan the following may occur, and the frequency may vary with the 
combinations of medicines that are received. 

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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) 
 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 
 tiredness; or flu-like symptoms 
 weight gain or loss. 
 
Common (may affect up to 1 in 10 people): 
 fungal infection of the mouth (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). 
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 inflammation of the colon, small intestine; intestinal perforation 
 blood clots. 
 
Frequency unknown: 
 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). 

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 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium in your blood. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Docetaxel Mylan 80 mg/4 ml 
 
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, dilution must take place in controlled and aseptic conditions. 
 
Use immediately the medicine once added into the non-PVC 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°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. 
 
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 Mylan 80 mg/4 ml contains  
 
The active substance is docetaxel. Each ml of concentrate for solution for infusion contains 20 mg 
docetaxel (anhydrous). 
One vial contains 80 mg of docetaxel. 
The other ingredients are polysorbate 80, ethanol anhydrous and citric acid.  
 
What Docetaxel Mylan 80 mg/4 ml looks like and contents of the pack 
 
Docetaxel Mylan concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a clear colourless glass vial with a rubber stopper and a plastic flip-off 
cap. 
Each vial contains 4 ml of concentrate. 
Each box contains 1 or 5 vials. 
 

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Marketing Authorisation Holder and Manufacturer 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00  
 

Lietuva 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

България 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00 (Belgium) 
 

Ceská republika 
MylanPharmaceuticals s.r.o. 
Tel: +420 274 770 201 
 

Magyarország 
Mylan Kft 
Tel: 36 1 8026993 

Danmark 
Mylan ApS  
Tlf: + 45 3694 4568  
 

Malta 
George Borg Barthet Ltd 
Tel: +356 21244205 
 

Deutschland 
Mylan dura GmbH  
Tel: + 49-(0) 6151 9512 0 
 

Nederland 
Mylan B.V 
Tel: + 31 (0)33 2997080 

Eesti 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Norge 
Mylan AB 
Tlf: + 46 8-555 227 50 (Sverige) 
 

Ελλάδα  
Generics Pharma Hellas ΕΠΕ  
Τηλ:  +30 210 9936410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 24 18 

España 
Mylan Pharmaceuticals, S.L 
tel: +  34 93 3786400 
 

Polska 
Mylan Sp.z.o.o 
Tel: +48 22 5466400 
 

France 
Mylan SAS 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Phone: + 00351 21 412 7200 
 

Hrvatska 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

România 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Ireland 
Mc Dermott Laboratories Ltd  
Tel: + 1800 272 272  
Allphar +353 1 4041600 
 

Slovenija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

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Ísland 
Mylan AB 
Tel: + 46 8-555 227 50 
 

Slovenská republika 
Mylan sr.o 
Tel: +421 2 32 604 901 
 

Italia 
Mylan S.p.A 
Tel: + +39/02-61246921 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: + 358 9-46 60 03  

Κύπρος 
Pharmaceutical Trading Co Ltd 
Τηλ: +35 7 24656165 
 

Sverige 
Mylan AB  
Tel: + 46 8-555 227 50 
 

Latvija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

United Kingdom 
Generics [UK] Ltd t/a Mylan 
Tel: +44 1707 853000 

 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL MYLAN CONCENTRATE FOR 
SOLUTION FOR INFUSION 
 

It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 

Mylan 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 Mylan 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 Mylan concentrate for solution for infusion, which 
contains only 1 vial). 
 
Docetaxel Mylan concentrate for solution for infusion requires NO prior dilution with a solvent 
and is ready to be added 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. 

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In Docetaxel Mylan, 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, 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. 
 

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Package Leaflet: Information for the user 

 
Docetaxel Mylan 200 mg/10 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 or hospital pharmacist. 
- 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 Mylan 200 mg/10 ml is and what it is used for 
2. What you need to know before you use Docetaxel Mylan 200 mg/10 ml 
3. How to use Docetaxel Mylan 200 mg/10 ml 
4. Possible side effects 
5. How to store Docetaxel Mylan 200 mg/10 ml 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Mylan is and what it is used for 
 
Docetaxel is a substance derived from the needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
Docetaxel Mylan 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 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 could be 
administered in combination with doxorubicin and cyclophosphamide. 
- For the treatment of lung cancer, docetaxel could be administered either alone or in combination with 
cisplatin. 
- For the treatment of prostate cancer, docetaxel is administered in combination with prednisone or 
prednisolone. 
- For the treatment of metastatic gastric cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
- For the treatment of head and neck cancer, docetaxel is administered in combination with cisplatin 
and 5-fluorouracil. 
 
 
2. What you need to know before you use Docetaxel Mylan 200 mg/10 ml 
 
You must not be given Docetaxel Mylan 
 
- if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel 

Mylan 
- if the number of white blood cells is too low. 
- if you have a severe liver disease. 
 

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Warnings and precautions 
 
Before each treatment with Docetaxel Mylan, you will have blood tests to check that you have enough 
blood cells and sufficient liver function to receive Docetaxel Mylan. In case of white blood cells 
disturbances, you may experience associated fever or infections. 
 
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. 
 
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 Mylan 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 Mylan 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. 
Docetaxel Mylan contains alcohol. Discuss with your doctor if you suffer from alcohol dependency or 
liver impairment. See also section “Docetaxel Mylan contains ethanol” below. 
 
Other medicines and Docetaxel Mylan 
 
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 Mylan or 
the other medicine may not work as well as expected and you may be more likely to get a side effect. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Mylan must NOT be administered if you are pregnant unless clearly indicated by your 
doctor. 
 
You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy, because Docetaxel Mylan 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 Mylan. 
 
If you are a man being treated with Docetaxel Mylan 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 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
Docetaxel Mylan contains ethanol 
 
This medicine contains 50 vol % ethanol (alcohol), i.e. up to 3.95g per vial equivalent to 100 ml of 
beer or 40 ml wine per vial. 
 
Harmful for those suffering from alcoholism. 
To be taken into account if you are pregnant or if you are 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 alter the effects of other medicines. 

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The amount of alcohol in this medicine may impair your ability to drive or use machines. 
 
 
3. How to use Docetaxel Mylan 200 mg/10 ml 
 
Docetaxel Mylan 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 Mylan 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 Mylan. 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. 
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 Mylan alone are: decrease in the number 
of red blood cells or white blood cells, hair loss, nausea, vomiting, sores in the mouth, diarrhoea and 
tiredness. 
 
The severity of adverse events of Docetaxel Mylan may be increased when Docetaxel Mylan is given 
in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions (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. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Mylan the following may occur, and the frequency may vary with the 
combinations of medicines that are received. 

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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) 
 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 
 tiredness; or flu-like symptoms 
 weight gain or loss. 
 
Common (may affect up to 1 in 10 people): 
 fungal infection of the mouth (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). 
 
Uncommon (may affect up to 1 in 100 people): 
 fainting 
 at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
 inflammation of the colon, small intestine; intestinal perforation 
 blood clots. 
 
Frequency unknown: 
 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). 

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 blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
 decrease of the sodium in your blood. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Docetaxel Mylan 200 mg/10 ml 
 
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, dilution must take place in controlled and aseptic conditions. 
 
Use immediately the medicine once added into the non-PVC 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°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. 
 
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 Mylan 200 mg/10 ml contains  
 
The active substance is docetaxel. Each ml of concentrate for solution for infusion contains 20 mg 
docetaxel (anhydrous). 
One vial contains 200 mg of docetaxel.  
The other ingredients are polysorbate 80, ethanol anhydrous and citric acid.  
 
What Docetaxel Mylan 200 mg/10 ml looks like and contents of the pack 
 
Docetaxel Mylan concentrate for solution for infusion is a pale yellow to brownish-yellow solution. 
The concentrate is supplied in a clear colourless glass vial with a rubber stopper and a plastic flip-off 
cap. 
Each vial contains 10 ml of concentrate. 
Each box contains 1 or 5 vials. 
 

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151 

Marketing Authorisation Holder and Manufacturer 
 
Mylan S.A.S. 
117 allée des parcs 
69800 Saint Priest 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00  
 

Lietuva 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

България 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tél/Tel: + 0032 2 658 61 00 (Belgium) 
 

Ceská republika 
MylanPharmaceuticals s.r.o. 
Tel: +420 274 770 201 
 

Magyarország 
Mylan Kft 
Tel: 36 1 8026993 

Danmark 
Mylan ApS  
Tlf: + 45 3694 4568  
 

Malta 
George Borg Barthet Ltd 
Tel: +356 21244205 
 

Deutschland 
Mylan dura GmbH  
Tel: + 49-(0) 6151 9512 0 
 

Nederland 
Mylan B.V 
Tel: + 31 (0)33 2997080 

Eesti 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Norge 
Mylan AB 
Tlf: + 46 8-555 227 50 (Sverige) 
 

Ελλάδα  
Generics Pharma Hellas ΕΠΕ  
Τηλ:  +30 210 9936410 
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 24 18 

España 
Mylan Pharmaceuticals, S.L 
tel: +  34 93 3786400 
 

Polska 
Mylan Sp.z.o.o 
Tel: +48 22 5466400 
 

France 
Mylan SAS 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Phone: + 00351 21 412 7200 
 

Hrvatska 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

România 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

Ireland 
Mc Dermott Laboratories Ltd  
Tel: + 1800 272 272  
Allphar +353 1 4041600 
 

Slovenija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

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Ísland 
Mylan AB 
Tel: + 46 8-555 227 50 
 

Slovenská republika 
Mylan sr.o 
Tel: +421 2 32 604 901 
 

Italia 
Mylan S.p.A 
Tel: + +39/02-61246921 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: + 358 9-46 60 03  

Κύπρος 
Pharmaceutical Trading Co Ltd 
Τηλ: +35 7 24656165 
 

Sverige 
Mylan AB  
Tel: + 46 8-555 227 50 
 

Latvija 
Mylan SAS 
Tel: +33 4 37 25 75 00 (France) 
 

United Kingdom 
Generics [UK] Ltd t/a Mylan 
Tel: +44 1707 853000 

 
This leaflet was last revised in {MM/YYYY}  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
PREPARATION GUIDE FOR USE WITH DOCETAXEL MYLAN CONCENTRATE FOR 
SOLUTION FOR INFUSION 
 

It is important that you read the entire contents of this guide prior to the preparation of the Docetaxel 

Mylan 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 Mylan 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 Mylan concentrate for solution for infusion, which 
contains only 1 vial). 
 
Docetaxel Mylan concentrate for solution for infusion requires NO prior dilution with a solvent 
and is ready to be added 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. 

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In Docetaxel Mylan, 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, 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. 
 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	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
	A. LABELLING
	B. PACKAGE LEAFLET
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the treatment of metastatic gastric cancer, docetaxel is administered in combination with cisplatin and 5-fluorouracil. - for the treatment of head and neck cancer, docetaxel is administered in combination with cisplatin and 5-fluorouracil.', 'Entity_Recognition': [{'Text': 'docetaxel mylan', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 13, 'BeginOffset': 0, 'EndOffset': 9, 'Score': 0.9996553659439087, 'Text': 'docetaxel', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 14, 'BeginOffset': 64, 'EndOffset': 73, 'Score': 0.9900974035263062, 'Text': 'docetaxel', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'anti-cancer medicines', 'Type': 'TREATMENT', 'BeginOffset': 98, 'EndOffset': 119}, {'Id': 15, 'BeginOffset': 127, 'EndOffset': 134, 'Score': 0.8079606890678406, 'Text': 'taxoids', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.2449498474597931, 'RelationshipScore': 0.9141492247581482, 'RelationshipType': 'FORM', 'Id': 17, 'BeginOffset': 146, 'EndOffset': 151, 'Text': 'mylan', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': 'docetaxel mylan', 'Type': 'TREATMENT', 'BeginOffset': 136, 'EndOffset': 151}, {'Id': 36, 'BeginOffset': 208, 'EndOffset': 221, 'Score': 0.9367973208427429, 'Text': 'breast cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.980885922908783}]}, {'Id': 37, 'BeginOffset': 240, 'EndOffset': 251, 'Score': 0.9258310794830322, 'Text': 'lung cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9808804392814636}]}, {'Id': 38, 'BeginOffset': 253, 'EndOffset': 279, 'Score': 0.9713984131813049, 'Text': 'non-small cell lung cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9835859537124634}]}, {'Id': 2, 'BeginOffset': 268, 'EndOffset': 272, 'Score': 0.974782407283783, 'Text': 'lung', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 39, 'BeginOffset': 282, 'EndOffset': 297, 'Score': 0.9230919480323792, 'Text': 'prostate cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.980387806892395}]}, {'Id': 40, 'BeginOffset': 299, 'EndOffset': 313, 'Score': 0.9791248440742493, 'Text': 'gastric cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9662603139877319}]}, {'Id': 41, 'BeginOffset': 317, 'EndOffset': 337, 'Score': 0.4294653832912445, 'Text': 'head and neck cancer', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9786152839660645}]}, {'Id': 5, 'BeginOffset': 326, 'EndOffset': 330, 'Score': 0.9844886064529419, 'Text': 'neck', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': 'advanced breast cancer', 'Type': 'PROBLEM', 'BeginOffset': 362, 'EndOffset': 384}, {'Id': 18, 'BeginOffset': 386, 'EndOffset': 395, 'Score': 0.9995008707046509, 'Text': 'docetaxel', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 19, 'BeginOffset': 454, 'EndOffset': 465, 'Score': 0.9994445443153381, 'Text': 'doxorubicin', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 20, 'BeginOffset': 470, 'EndOffset': 481, 'Score': 0.9991208910942078, 'Text': 'trastuzumab', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 21, 'BeginOffset': 486, 'EndOffset': 498, 'Score': 0.9993732571601868, 'Text': 'capecitabine', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'early breast cancer', 'Type': 'PROBLEM', 'BeginOffset': 523, 'EndOffset': 542}, {'Text': 'lymph node involvement', 'Type': 'PROBLEM', 'BeginOffset': 559, 'EndOffset': 581}, {'Id': 22, 'BeginOffset': 583, 'EndOffset': 592, 'Score': 0.999269425868988, 'Text': 'docetaxel', 'Category': 'MEDICATION', 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{'Title': '2. what you need to know before you use docetaxel mylan 20 mg/1 ml', 'Section_Content': 'you must not be given docetaxel mylan - if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of docetaxel mylan - if the number of white blood cells is too low. - if you have a severe liver disease. warnings and precautions before each treatment with docetaxel mylan, you will have blood tests to check that you have enough blood cells and sufficient liver function to receive docetaxel mylan. in case of white blood cells disturbances, you may experience associated fever or infections. 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. 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 mylan 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 mylan 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. docetaxel mylan contains alcohol. discuss with your doctor if you suffer from alcohol dependency or liver impairment. see also section "docetaxel mylan contains ethanol" below. other medicines and docetaxel mylan 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 mylan or the other medicine may not work as well as expected and you may be more likely to get a side effect. pregnancy, breast-feeding and fertility ask your doctor for advice before being given any medicine. docetaxel mylan must not be administered if you are pregnant unless clearly indicated by your doctor. you must not become pregnant during treatment with this medicine and must use an effective method of contraception during therapy, because docetaxel mylan 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 mylan. if you are a man being treated with docetaxel mylan 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 no studies on the effects on the ability to drive and use machines have been performed. docetaxel mylan contains ethanol this medicine contains 50 vol % ethanol (alcohol), i.e. up to 0.395 g per vial equivalent to 10 ml of beer or 4 ml wine per vial. harmful for those suffering from alcoholism. to be taken into account if you are pregnant or if you are 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 alter the effects of other medicines. the amount of alcohol in this medicine may impair your ability to drive or use machines.', 'Entity_Recognition': [{'Text': 'docetaxel mylan', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'docetaxel mylan', 'Type': 'TREATMENT', 'BeginOffset': 22, 'EndOffset': 37}, {'Id': 34, 'BeginOffset': 51, 'EndOffset': 75, 'Score': 0.36243143677711487, 'Text': 'allergic (hypersensitive', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.7152493000030518}]}, {'Id': 10, 'BeginOffset': 80, 'EndOffset': 89, 'Score': 0.9995858073234558, 'Text': 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{'Title': '3. how to use docetaxel mylan 20 mg/1 ml', 'Section_Content': 'docetaxel mylan 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 mylan 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 mylan. 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.', 'Entity_Recognition': [{'Text': 'docetaxel mylan', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'docetaxel mylan', 'Type': 'TREATMENT', 'BeginOffset': 0, 'EndOffset': 15}, {'Text': 'your weight', 'Type': 'TEST', 'BeginOffset': 109, 'EndOffset': 120}, {'Text': 'method', 'Type': 'TREATMENT', 'BeginOffset': 269, 'EndOffset': 275}, {'Text': 'administration docetaxel mylan', 'Type': 'TREATMENT', 'BeginOffset': 289, 'EndOffset': 319}, {'Id': 0, 'BeginOffset': 363, 'EndOffset': 368, 'Score': 0.7564136981964111, 'Text': 'veins', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': 'the infusion', 'Type': 'TREATMENT', 'BeginOffset': 388, 'EndOffset': 400}, {'Id': 14, 'BeginOffset': 425, 'EndOffset': 433, 'Score': 0.6229149699211121, 'Text': 'one hour', 'Category': 'TIME_EXPRESSION', 'Type': 'TIME_TO_TREATMENT_NAME', 'Traits': [], 'Attributes': [{'Type': 'TREATMENT_NAME', 'Score': 0.3097318708896637, 'RelationshipScore': 0.8152279257774353, 'RelationshipType': 'OVERLAP', 'Id': 10, 'BeginOffset': 392, 'EndOffset': 400, 'Text': 'infusion', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Traits': []}]}, {'Text': 'your infusion', 'Type': 'TREATMENT', 'BeginOffset': 531, 'EndOffset': 544}, {'Id': 15, 'BeginOffset': 550, 'EndOffset': 563, 'Score': 0.8528961539268494, 'Text': 'every 3 weeks', 'Category': 'TIME_EXPRESSION', 'Type': 'TIME_TO_TREATMENT_NAME', 'Traits': [], 'Attributes': [{'Type': 'TREATMENT_NAME', 'Score': 0.5610911846160889, 'RelationshipScore': 0.8532312512397766, 'RelationshipType': 'OVERLAP', 'Id': 11, 'BeginOffset': 536, 'EndOffset': 544, 'Text': 'infusion', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Traits': []}]}, {'Text': '3', 'Type': 'NUMBER', 'BeginOffset': 556, 'EndOffset': 557}, {'Text': 'your blood tests', 'Type': 'TEST', 'BeginOffset': 634, 'EndOffset': 650}, {'Text': 'your general condition', 'Type': 'PROBLEM', 'BeginOffset': 652, 'EndOffset': 674}, {'Text': 'docetaxel mylan', 'Type': 'TREATMENT', 'BeginOffset': 696, 'EndOffset': 711}, {'Id': 6, 'BeginOffset': 765, 'EndOffset': 774, 'Score': 0.955357015132904, 'Text': 'diarrhoea', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.559540867805481}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9781525731086731, 'RelationshipScore': 0.7646459341049194, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 1, 'BeginOffset': 789, 'EndOffset': 794, 'Text': 'mouth', 'Category': 'ANATOMY', 'Traits': []}]}, {'Text': 'sores in the mouth', 'Type': 'PROBLEM', 'BeginOffset': 776, 'EndOffset': 794}, {'Id': 8, 'BeginOffset': 807, 'EndOffset': 815, 'Score': 0.968559741973877, 'Text': 'numbness', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8564665913581848}]}, {'Text': 'pins and needles', 'Type': 'PROBLEM', 'BeginOffset': 819, 'EndOffset': 835}, {'Id': 9, 'BeginOffset': 837, 'EndOffset': 842, 'Score': 0.8633835911750793, 'Text': 'fever', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.6876005530357361}]}, {'Text': 'your blood tests', 'Type': 'TEST', 'BeginOffset': 871, 'EndOffset': 887}, {'Text': 'a dose reduction', 'Type': 'TREATMENT', 'BeginOffset': 943, 'EndOffset': 959}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 1019, 'EndOffset': 1032}]}
{'Title': '4. possible side effects', 'Section_Content': '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 mylan alone are: decrease in the number of red blood cells or white blood cells, hair loss, nausea, vomiting, sores in the mouth, diarrhoea and tiredness. the severity of adverse events of docetaxel mylan may be increased when docetaxel mylan is given in combination with other chemotherapeutic agents. during the infusion at the hospital the following allergic reactions (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. the hospital staff will monitor your condition closely during treatment. tell them immediately if you notice any of these effects. between infusions of docetaxel mylan 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) 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 tiredness; or flu-like symptoms weight gain or loss. common (may affect up to 1 in 10 people): fungal infection of the mouth (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). uncommon (may affect up to 1 in 100 people): fainting at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling inflammation of the colon, small intestine; intestinal perforation blood clots. frequency unknown: 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 in your blood. reporting of side effects if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'docetaxel mylan', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, 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