Taxespira

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

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1. NAME OF THE MEDICINAL PRODUCT

Taxespira 20 mg/1 ml concentrate for solution for infusion
Taxespira 80 mg/4 ml concentrate for solution for infusion
Taxespira 120 mg/6 ml concentrate for solution for infusion
Taxespira 140 mg/7 ml concentrate for solution for infusion
Taxespira 160 mg/8 ml concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of concentrate contains 20 mg docetaxel (as trihydrate). 

20mg/1 ml 
One vial of 1 ml of concentrate contains 20 mg docetaxel.

80mg/4 ml
One vial of 4 ml concentration contains 80 mg docetaxel.

120mg/6 ml
One vial of 6 ml concentration contains 120 mg docetaxel.  

140mg/7 ml
One vial of 7 ml concentration contains 140 mg docetaxel.  

160mg/8 ml
One vial of 8 ml concentration contains 160 mg docetaxel.  

Excipient with known effect

20mg/1 ml
Each 1 ml vial of concentrate contains 0.5 ml of ethanol anhydrous (395 mg). 

80mg/4 ml
Each 4 ml vial of concentrate contains 2 ml of ethanol anhydrous (1580 mg).

120mg/6 ml
Each 6 ml vial of concentrate contains 3 ml of ethanol anhydrous (2370 mg). 

140mg/7 ml
Each 7 ml vial of concentrate contains 3.5 ml of ethanol anhydrous (2765 mg). 

160mg/8 ml
Each 8 ml vial of concentrate contains 4 ml of ethanol anhydrous (3160 mg). 

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for solution for infusion. 

The concentrate is a pale yellow to brownish-yellow solution.

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4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Breast cancer
Taxespira 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). 

Taxespira 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. 

Taxespira 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. 

Taxespira 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. 

Taxespira 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. 

Non-small cell lung cancer
Taxespira is indicated for the treatment of patients with locally advanced or metastatic non-small cell 
lung cancer after failure of prior chemotherapy. 

Taxespira 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
Taxespira in combination with prednisone or prednisolone is indicated for the treatment of patients 
with hormone refractory metastatic prostate cancer. 

Gastric adenocarcinoma
Taxespira 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
Taxespira 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). 

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Posology
For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral 
corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to 
docetaxel administration, unless contraindicated, can be used (see section 4.4). 

For 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). 

Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities.

Docetaxel is administered as a one-hour infusion every three weeks. 

Breast cancer
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the 
recommended dose of docetaxel is 75 mg/m2 administered 1-hour after doxorubicin 50 mg/m2 and 
cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments 
during treatment). 

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy. In first-line treatment, docetaxel 75 mg/m2 is given in 
combination therapy with doxorubicin (50 mg/m2). 

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m2 every three weeks, 
with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started 
the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered 
immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was 
well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product 
characteristics. 

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m2 every three weeks, 
combined with capecitabine at 1250 mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks 
followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, 
see capecitabine summary of product characteristics. 

Non-small cell lung cancer
In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen
is docetaxel 75 mg/m2 immediately followed by cisplatin 75 mg/m2 over 30-60 minutes. For treatment 
after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single 
agent. 

Prostate cancer 
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 

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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 
60 mg/m². If the patient continues to experience these reactions at 60 mg/m2, the treatment should be 
discontinued. 

Adjuvant therapy for breast cancer
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and 
cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile 
neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m2 in all 
subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should 
have their dose decreased to 60 mg/m2. 

In combination with cisplatin
For patients who are dosed initially at docetaxel 75 mg/m2 in combination with cisplatin and whose 
nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, or in patients who 
experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel 
dose in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dose adjustments, see the 
corresponding summary of product characteristics. 

In combination with capecitabine
 For capecitabine dose modifications, see capecitabine summary of product characteristics. 
 For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the 

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

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

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 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 
>1,500cells/mm3 and platelets recover to a level >100,000 cells/mm3. Treatment must be discontinued
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. 

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 (e.g., 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 Taxespira in nasopharyngeal carcinoma in children aged 1 month to less 
than 18 years have not yet been established. 

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There is no relevant use of Taxespira in the paediatric population for the indication of 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. 

Elderly
Based on a population pharmacokinetic analysis, there are no special instructions for use in the
elderly.

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of 
capecitabine to 75% is recommended (see capecitabine summary of product characteristics).

Method of administration
For instructions on preparation and administration of the product, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Patients with baseline neutrophil count of <1,500 cells/mm3. 

Patients with severe liver impairment (see sections 4.2 and 4.4). 

Contraindications for other medicinal products also apply, when combined with docetaxel.

4.4 Special warnings and precautions for use

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as 
dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel 
administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well 
as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral 
dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2). 

Haematology
Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median 
of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of 
complete blood counts should be conducted on all patients receiving docetaxel. Patients should be 
retreated with docetaxel when neutrophils recover to a level ≥ 1,500 cells/mm3 (see section 4.2). 

In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of 
docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate 
symptomatic measures are recommended (see section 4.2). 

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile 
neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic 
G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of 
complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). 
Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8). 

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), 
febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received 
primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive 
adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile 
neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be 
closely monitored (see sections 4.2 and 4.8). 

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Gastrointestinal reactions

Caution is recommended for patients with neutropenia, particularly at risk for developing 
gastrointestinal complications. Although majority of cases occurred during the first or second cycle of 
docetaxel containing regimen, enterocolitis could develop at any time, and could lead to death as early 
as on the first day of onset. Patients should be closely monitored for early manifestations of serious 
gastrointestinal toxicity (see sections 4.2, 4.4 Haematology, and 4.8).

Hypersensitivity reactions
Patients should be observed closely for hypersensitivity reactions especially during the first and 
second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 
of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. Patients who have previously experienced a 
hypersensitivity reaction to paclitaxel may be at risk to develop hypersensitivity reaction to docetaxel, 
including more severe hypersensitivity reaction. These patients should be closely monitored during 
initiation of docetaxel therapy.

Cutaneous reactions
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 
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 

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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.

Ventricular arrhythmia including ventricular tachycardia (sometimes fatal) has been reported in 
patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or 
cyclophosphamide (see section 4.8). 

Baseline cardiac assessment is recommended.

Eye disorders
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 
4.8). 

Others
Contraceptive measures must be taken by both men and women during treatment and for men at least 
6 months after cessation of therapy (see section 4.6). 

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, 
clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and 
voriconazole) should be avoided (see section 4.5).

Additional cautions for use in adjuvant treatment of breast cancer

Complicated neutropenia
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 

Gastrointestinal reactions
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 

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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). 

Elderly people
There are limited data available 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 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

20mg/1 ml: 
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol 
anhydrous per 1 ml vial. This is equivalent to 10 ml of beer or 4 ml of wine. 

80mg/4 ml:
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1580 mg ethanol 
anhydrous per 4 ml vial. This is equivalent to 40 ml of beer or17 ml of wine.

120mg/6 ml:
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2370 mg ethanol 
anhydrous per 6 ml vial. This is equivalent to 60 ml of beer or 25 ml of wine.

140mg/7 ml:
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2765 mg ethanol 
anhydrous per 7 ml vial. This is equivalent to 70 ml of beer or 29 ml of wine.

160mg/8 ml:
This medicinal product contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3160 mg ethanol 
anhydrous per 8 ml vial. This is equivalent to 80 ml of beer or 33 ml of wine.

Harmful for those suffering from alcoholism. 

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To be taken into account in pregnant or breast-feeding women, in children and in high-risk groups 
such as patients with liver disease, or epilepsy. 
Consideration should be given to possible effects on the central nervous system.

4.5 Interaction with other medicinal products and other forms of interaction

The amount of alcohol in this medicinal product may alter the effects of other medicinal products.

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as ciclosporine, ketoconazole and erythromycin. As 
a result, caution should be exercised when treating patients with these medicinal products as 
concomitant therapy since there is a potential for a significant interaction. 

In case of combination with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may 
increase, as a result of reduced metabolism. If the concomitant use of a strong CYP3A4 inhibitor (e.g., 
ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, 
telithromycin and voriconazole) cannot be avoided, a close clinical surveillance is warranted and a 
dose-adjustment of docetaxel may be suitable during the treatment with the strong CYP3A4 inhibitor 
(see section 4.4). In a pharmacokinetic study with 7 patients, the co-administration of docetaxel with 
the strong CYP3A4 inhibitor ketoconazole leads to a significant decrease in docetaxel clearance by 
49%. 

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic 
prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. 
No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed. 

Docetaxel is highly protein bound (>95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal product has not been investigated formally, in vitro interactions 
with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, 
phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of 
docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not 
influence the binding of digitoxin. 

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their 
co-administration. Limited data from a single uncontrolled study were suggestive of an interaction 
between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was 
about 50% higher than values previously reported for carboplatin monotherapy. 

4.6 Fertility, pregnancy and lactation

Pregnancy
There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 
both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other 
cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated. 

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 

Breast-feeding
Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 
Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 
discontinued for the duration of docetaxel therapy. 

Contraception in males and females
An effective method of contraception should be used during treatment. 

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Fertility
In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). 
Therefore, men being treated with docetaxel are advised not to father a child during and up to 
6 months after treatment and to seek advice on conservation of sperm prior to treatment

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. The amount of 
alcohol in this medicinal product and the side effects of the product may impair the ability to drive or 
use machines (see sections 4.4 and 4.8). Therefore, patients should be warned of the potential impact 
of the amount of alcohol and the side effects of this medicinal product on the ability to drive or use 
machines, and be advised not to drive or use machines if they experience these side effects during 
treatment.

4.8 Undesirable effects

Summary of the safety profile for all indications
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in: 
 1,312 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). 
 1,276 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. 

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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. 
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 paraesthesia, 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 Taxespira 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: 

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MedDRA system 
organ classes

Very common adverse 
reactions

Common adverse 
reactions

Uncommon adverse 
reactions

0.07%) 
Cardiac disorders Arrhythmia (G3/4: 

0.7%) 
Cardiac failure 

Vascular disorders Hypotension; 
Hypertension; 
Haemorrhage 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe: 
2.7%) 

Gastrointestinal 
disorders 

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

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

Oesophagitis (severe: 
0.4%) 

Skin and subcutaneous 
tissue disorders 

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

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 1.4%) Arthralgia 

General disorders and 
administration site 
conditions 

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

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

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

Description of selected adverse reactions in breast cancer for Taxespira 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 Taxespira 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 Taxespira 75 mg/m² in combination with 
doxorubicin

MedDRA system 
organ classes

Very common adverse 
reactions

Common adverse 
reactions

Uncommon adverse 
reactions

Infections and 
infestations 

Infection (G3/4: 7.8%) 

Blood and lymphatic 
system disorders 

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

Immune system 
disorders 

Hypersensitivity (G3/4: 
1.2%) 

Metabolism and 
nutrition disorders 

Anorexia 

Nervous system 
disorders 

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy (G3/4: 
0.4%) 

Cardiac disorders Cardiac failure; 
Arrhythmia (no severe) 

Vascular disorders Hypotension 
Gastrointestinal 
disorders 

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

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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 Taxespira 75 mg/m² in 
combination with cisplatin

MedDRA system 
organ classes

Very common 
adverse reactions

Common adverse 
reactions

Uncommon adverse
reactions

Infections and 
infestations 

Infection (G3/4: 5.7%) 

Blood and lymphatic 
system disorders 

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

Febrile neutropenia 

Immune system 
disorders 

Hypersensitivity 
(G3/4: 2.5%) 

Metabolism and 
nutrition disorders 

Anorexia 

Nervous system 
disorders 

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

Cardiac disorders Arrhythmia (G3/4: 
0.7%) 

Cardiac failure 

Vascular disorders Hypotension (G3/4: 
0.7%) 

Gastrointestinal 
disorders 

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

Constipation 

Skin and 
subcutaneous tissue 
disorders 

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

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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 Taxespira 100 mg/m² in combination with 
trastuzumab

MedDRA system organ classes Very common adverse reactions Common adverse reactions
Blood and lymphatic system 
disorders 

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

Metabolism and nutrition 
disorders 

Anorexia 

Psychiatric disorders Insomnia 
Nervous system disorders Paresthesia; Headache; Dysgeusia; 

Hypoaesthesia 
Eye disorders Lacrimation increased; 

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

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

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

Skin and subcutaneous tissue 
disorders 

Alopecia; Erythema; Rash; Nail 
disorders 

Musculoskeletal and connective 
tissue disorders 

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

General disorders and 
administration site conditions 

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

Lethargy 

Investigations Weight increased 

Description of selected adverse reactions in breast cancer for Taxespira 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. 

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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 Taxespira 75 mg/m² in combination with 
capecitabine

MedDRA system organ classes Very common adverse reactions Common adverse reactions
Infections and infestations Oral candidiasis (G3/4: 

<1%) 
Blood and lymphatic system 
disorders 

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

Thrombocytopenia (G3/4: 
3%) 

Metabolism and nutrition 
disorders 

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

Dehydration (G3/4: 2%) 

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

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

Eye disorders Lacrimation increased 
Respiratory, thoracic and 
mediastinal disorders 

Pharyngolaryngeal pain (G3/4: 2%) Dyspnoea (G3/4: 1%); 
Cough (G3/4: <1%); 
Epistaxis (G3/4: <1%) 

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

Abdominal pain upper; Dry 
mouth 

Skin and subcutaneous tissue 
disorders 

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

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

Musculoskeletal and connective 
tissue disorders 

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

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

General disorders and 
administration site conditions 

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

Lethargy; 
Pain 

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

Tabulated list of adverse reactions in prostate cancer for Taxespira 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 Peripheral motor neuropathy 

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(G3/4: 1.2%); Dysgeusia (G3/4: 
0%) 

(G3/4: 0%) 

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

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

Respiratory, thoracic and 
mediastinal disorders 

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

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

Skin and subcutaneous tissue 
disorders 

Alopecia; Nail disorders (no 
severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
bone disorders 

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

General disorders and 
administration site conditions 

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

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

Abdominal pain 
(G3/4: 0.4%) 

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Vomiting (G3/4: 4.2%); 
Diarrhoea (G3/4: 3.4%); 
Constipation (G3/4: 
0.5%) 

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%) 

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

Description of selected adverse reactions for adjuvant therapy with Taxespira 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer 

Nervous system disorders
In study TAX316, peripheral sensory neuropathy started during the treatment period and persisted into 
the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2 %) in FAC arm. At the end 
of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was 
observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. In 
GEICAM 9805 study, peripheral sensory neuropathy that started during the treatment period persisted 
into the follow-up period in 10 patients (1.9%) in TAC arm and 4 patients (0.8 %) in FAC arm. At the 
end of the follow-up period (median follow-up time of 10 years and 5 months), peripheral sensory 
neuropathy was observed to be ongoing in 3 patients (0.6%) in TAC arm, and in 1 patient (0.2%) in 
FAC arm.

Cardiac disorders
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure. All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period. Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
In GEICAM 9805 study, 3 patients (0.6 %) in TAC arm and 3 patients (0.6 %) in FAC arm developed 
congestive heart failure during the follow-up period. At the end of the follow-up period (actual median 
follow-up time of 10 years and 5 months), no patients had CHF in TAC arm and 1 patient in TAC arm 
died because of dilated cardiomyopathy and CHF was observed to be ongoing in 1 patient (0.2%) in 
FAC arm.

Skin and subcutaneous tissue disorders
In study TAX316 alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). 
At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to 
be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).

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In GEICAM 9805 study alopecia that started during the treatment period and persisted into the follow-
up period was observed to be ongoing in 49 patients (9.2 %) in TAC arm and 35 patients (6.7 %) in 
FAC arm. Alopecia related to study drug started or worsened during the follow-up period in 42 
patients (7.9 %) in TAC arm and 30 patients (5.8 %) in FAC arm. At the end of the follow-up period 
(median follow-up time of 10 years and 5 months), alopecia was observed to be ongoing in 3 patients 
(0.6%) in TAC arm, and in 1 patient (0.2%) in FAC arm.

Reproductive system and breast disorders
In study TAX316 amenorrhoea that started during the treatment period and persisted into the follow-
up period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 
736 FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period 
(median follow-up time of 8 years) in 121 patients of 744 TAC patients (16.3 %) and 86 FAC patients 
(11.7%).
In GEICAM 9805 study amenorrhoea that started during the treatment period and persisted into the 
follow-up period and was observed to be ongoing in 18 patients (3.4 %) in TAC arm and 5 patients 
(1.0 %) in FAC arm. At the end of the follow-up period (median follow-up time of 10 years and 5 
months), amenorrhoea was observed to be ongoing in 7 patients (1.3%) in TAC arm, and in 4 patients 
(0.8%) in FAC arm.

General disorders and administration site conditions
In study TAX316, peripheral oedema that started during the treatment period and persisted into the 
follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 
23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 
years), peripheral oedema was ongoing in 19 TAC patients and 4 FAC patients (0.5%).
In study TAX316 lymphoedema that started during the treatment period and persisted into the follow-
up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 
FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), 
lymphoedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%).
In study TAX316 asthenia that started during the treatment period and persisted into the follow-up 
period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 
FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), 
asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).

In study GEICAM 9805 peripheral oedema that started during the treatment period persisted into the 
follow-up period in 4 patients (0.8%) in TAC arm and in 2 patients (0.4%) in FAC arm. At the end of 
the follow-up period (median follow-up time of 10 years and 5 months), no patients (0%) in TAC arm 
had peripheral oedema and it was observed to be ongoing in 1 patient (0.2%) in FAC arm.
Lymphoedema that started during the treatment period persisted into the follow-up period in 5 patients 
(0.9%) in TAC arm and 2 patients (0.4 %) in FAC arm. At the end of the follow-up period, 
lymphoedema was observed to be ongoing in 4 patients (0.8%) in TAC arm, and in 1 patient (0.2%) in 
FAC arm. 

Asthenia that started during the treatment period and persisted into the follow-up period was observed 
to be ongoing in 12 patients (2.3 %) in TAC arm and 4 patients (0.8 %) in FAC arm. At the end of the 
follow-up period, asthenia was observed to be ongoing in 2 patients (0.4%) in TAC arm, and in 2 
patients (0.4%) in FAC arm.

Acute leukaemia /Myelodysplastic syndrome
After 10 years of follow up in study TAX316, acute leukaemia was reported in 3 of 744 TAC patients
(0.4%) and in 1 of 736 FAC patients (0.1%). One TAC patient (0.1%) and 1 FAC patient (0.1%) died 
due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic 
syndrome was reported in 2 of 744 TAC patients (0.3%) and in 1 of 736 FAC patients (0.1%). 

After 10 years of follow-up in GEICAM 9805 study, acute leukaemia occurred in 1 of 532
(0.2%)patients in TAC arm. No cases were reported in patients in FAC arm. No patient was diagnosed 
with myelodysplastic syndrome in either treatment groups.

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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 Taxespira 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/odynophagia 
(G3/4: 0.7%) 

Skin and subcutaneous tissue 
disorders 

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

General disorders and 
administration site conditions 

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

Description of selected adverse reactions in gastric adenocarcinoma cancer for Taxespira 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 

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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 Taxespira 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; 
Oesophagitis/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 

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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 
Gastrointestinal 
disorders 

Nausea (G3/4: 13.9%); 
Stomatitis (G3/4: 
20.7%); Vomiting 
(G3/4: 8.4%); Diarrhoea 
(G3/4: 6.8%); 
Oesophagitis/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 

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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.
Hypersensitivity reactions (frequency not known) have been reported with docetaxel in patients who 
previously experienced hypersensitivity reactions to paclitaxel.

Nervous system disorders
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 
administration. These reactions sometimes appear during the infusion of the medicinal product. 

Eye disorders
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 
during infusion of the medicinal product and in association with hypersensitivity reactions have been 
reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 
without conjunctivitis, as cases of lacrimal duct obstruction resulting in excessive tearing have been 
rarely reported. Cases of cystoid macular oedema (CMO) have been reported in patients treated with 
docetaxel. 

Ear and labyrinth disorders
Rare cases of ototoxicity, hearing impaired and/or hearing loss have been reported. 

Cardiac disorders
Rare cases of myocardial infarction have been reported.
Ventricular arrhythmia including ventricular tachycardia (frequency not known), sometimes fatal, has 
been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-
fluorouracil and/ or cyclophosphamide.

Vascular disorders
Venous thromboembolic events have rarely been reported. 

Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome and cases of interstitial pneumonia/pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 

Gastrointestinal disorders
Rare cases of enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, have been 
reported with a potential fatal outcome (frequency not known).

Rare occurrences of dehydration have been reported as a consequence of gastrointestinal events
including enterocolitis and gastrointestinal perforation.

Rare cases of ileus and intestinal obstruction have been reported. 

Hepatobiliary disorders
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 

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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 
permanent alopecia (frequency not known) have been reported. 

Renal and urinary disorders
Renal insufficiency and renal failure have been reported. In about 20% of these cases there were no 
risk factors for acute renal failure such as concomitant nephrotoxic medicinal products and 
gastro-intestinal disorders. 

General disorders and administration site conditions
Radiation recall phenomena have rarely been reported.
Injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following 
administration of docetaxel at a different site) has been observed at the site of previous extravasation 
(frequency not known).
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 

Metabolism and nutrition disorders
Cases of electrolyte imbalance have been reported. Cases of hyponatraemia have been reported, 
mostly associated with dehydration, vomiting and pneumonia. Hypokalaemia, hypomagnesaemia, and 
hypocalcaemia were observed, usually in association with gastrointestinal disorders and in particular 
with diarrhoea.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: 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

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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

Taxespira 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+), 1,491
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 OS was the 
secondary efficacy endpoint. 

A final analysis was performed with an actual median follow up of 96 months. Significantly longer 
disease-free survival for the TAC arm compared to the FAC arm was demonstrated. Incidence of 
relapses at 10 years was reduced in patients receiving TAC compared to those who received FAC 
(39% versus 45%, respectively) i.e. an absolute risk reduction by 6% (p = 0.0043). OS at 10 years was 
also significantly increased with TAC compared to FAC (76% versus 69%, respectively) i.e. an 
absolute reduction of the risk of death by 7% (p = 0.002). As the benefit observed in patients with 4 + 
nodes was not statistically significant on DFS and OS, the positive benefit/risk ratio for TAC in 
patients with 4 + nodes was not fully demonstrated at the final analysis. 

Overall, the study results demonstrate a positive benefit risk ratio for TAC compared to FAC. 

TAC-treated patient subsets according to prospectively defined major prognostic factors were 
analysed: 

Disease free survival Overall survival
Patient 
subset

Number 
of 
patients

Hazard 
ratio*

95% CI p = Hazard 
ratio*

95% CI p =

No of 
positive 

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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 
OS compared to FAC 

Patients with operable node-negative breast cancer eligible to receive chemotherapy (GEICAM 9805)

Data from a multicenter open label randomized trial support the use of Taxespira for the adjuvant 
treatment of patients with operable node-negative breast cancer eligible to receive chemotherapy. 1060 
patients were randomized to receive either Taxespira 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. Taxespira 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 OS was the secondary 
efficacy endpoint. 

At the median follow-up time of 77 months, significantly longer disease-free survival for the TAC arm 
compared to the FAC arm was demonstrated. TAC-treated patients had a 32% reduction in the risk of 
relapse compared to those treated with FAC (hazard ratio = 0.68, 95% CI (0.49-0.93), p = 0.01).At the 
median follow up time of 10 years and 5 months, TAC-treated patients had a 16.5% reduction in the 
risk of relapse compared to those treated with FAC (hazard ratio = 0.84, 95% CI (0.65-1.08), 
p=0.1646). DFS data were not statistically significant but were still associated with a positive trend in 
favour of TAC. 

At the median follow-up time of 77 months, 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 
analysed 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)

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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 260 0.67 0.43-1.05
≥50 years 279 0.67 0.43-1.05
Age category 2
<35 years 42 0.31 0.11-0.89
≥35 years 497 0.73 0.52-1.01
Hormonal receptor 
status
Negative 195 0.7 0.45-1.1
Positive 344 0.62 0.4-0.97
Tumour size 
≤2 cm 285 0.69 0.43-1.1
>2 cm 254 0.68 0.45-1.04
Histological grade
Grade1 (includes grade 
not assessed) 

64 0.79 0.24-2.6

Grade 2 216 0.77 0.46-1.3
Grade 3 259 0.59 0.39-0.9
Menopausal status
Pre-Menopausal 285 0.64 0.40-1
Post-Menopausal 254 0.72 0.47-1.12
*a hazard ratio (TAC/FAC) of less than 1 indicates that TAC is associated with a longer disease free 
survival compared to FAC. 

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

TAC FAC Hazard ratio
(TAC/FAC)

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

No 18/214
(8.4%)

26/227
(11.5%)

0.796 
(0.434 - 1.459)

0.4593

Yes 48/325
(14.8%)

69/294
(23.5%)

0.606 
(0.42 - 0.877)

0.0072

TAC = docetaxel, doxorubicin and cyclophosphamide 
FAC = 5-fluorouracil, doxorubicin and cyclophosphamide 
CI = confidence interval; ER = estrogen receptor 
PR = progesterone receptor 
a ER/PR-negative or Grade 3 or tumour size >5 cm 

The estimated hazard ratio was using Cox proportional hazard model with treatment group as the 
factor. 

Taxespira 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. 

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In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting OS 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 OS (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%). 

Taxespira 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. 

Taxespira 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 

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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 

Taxespira 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 
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 OS 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. 

Taxespira in combination with platinum agents in chemotherapy-naïve patients
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml.min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2

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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

OS
(Primary end-point): 

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

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

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

Median time to progression 
(weeks): 22.0 23.0 Hazard Ratio: 1.032

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

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

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

291
45.4

282
47.9

300
31.7

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95% CI 
p-value* 

(39.5-51.3)
0.0005

(41.9-53.9)
<0.0001

(26.4-37.3)
--

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

153
34.6

(27.1-42.7)
0.0107

154
31.2

(24.0-39.1)
0.0798

157
21.7

(15.5-28.9)
--

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

141
12.1

(7.2-18.6)
0.1112

134
8.2

(4.2-14.2)
0.5853

137
6.6

(3.0-12.1)
--

†Stratified log rank test 
*Threshold for statistical significance = 0.0175 
**PSA: Prostate-Specific Antigen 

Given the fact that docetaxel every week presented a slightly better safety profile than docetaxel every 
3 weeks, it is possible that certain patients may benefit from docetaxel every week. 

No statistical differences were observed between treatment groups for Global Quality of Life. 

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 
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. OS 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. 

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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). 
Patients on the comparator arm received cisplatin (P) 100 mg/m2 followed by 5-fluorouracil (F) 
1,000 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 OS 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 (%) 67.8 53.6

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(95% CI) (60.4-74.6) (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). 

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) 1,000 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) 1,000 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, OS was significantly longer 
(log-rank test, p = 0.0058) with the docetaxel-containing regimen compared to PF (median OS: 70.6 

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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 OS (months) 
(95% CI) 

70.6
(49.0-NA)

30.1
(20.9-51.5)

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

0.70
(0.54-0.90)

0.0058
Median PFS (months) 
(95% CI) 

35.5
(19.3-NA)

13.1
(10.6 - 20.2)

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

0.71
(0.56 - 0.90)

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

71.8
(65.8-77.2)

64.2
(57.9-70.2)

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

76.5
(70.8-81.5)

71.5
(65.5-77.1)

***p-value 0.209

A hazard ratio of less than 1 favours docetaxel + cisplatin + fluorouracil 
*un-adjusted log-rank test 
**un-adjusted log-rank test, not adjusted for multiple comparisons 
***Chi square test, not adjusted for multiple comparisons 
NA-not applicable 

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with 
Taxespira in all subsets of the paediatric population in breast cancer, non-small cell lung cancer, 
prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less 
differentiated nasopharyngeal carcinoma (see section 4.2 for information on paediatric use).

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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). 

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. 

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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

Polysorbate 80
Ethanol (anhydrous)
Citric acid monohydrate

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.

6.3 Shelf life

Unopened vial
24 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, reconstitution/dilution must take place in controlled and aseptic 
conditions and the medicinal product should be used immediately. If not used immediately, in-use 
storage times and conditions are the responsibility of the user.

Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored below 
25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour infusion 
intravenous administration).

In addition, physical and chemical in-use stability of the infusion solution prepared with sodium 
chloride 9 mg/ml (0.9%) or 5% glucose infused solution in non-PVC bags or with 5% glucose in glass 

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bottles has been demonstrated for up to 48 hours when stored between 2°C to 8°C and for up to 
6 hours when stored below 25°C.

Docetaxel infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, 
the solution must no longer be used and shall be discarded.

6.4 Special precautions for storage

Do not store above 25°C. 

Store in the original package in order to protect from light. 

For storage conditions of the diluted medicinal product, see section 6.3.

6.5 Nature and contents of container 

Clear glass (type I) vial with a chlorobutyl rubber stopper and an aluminium seal with a flip-off cap.

20mg/1 ml contains 1 ml of concentrate.

80mg/4 ml contains 4 ml of concentrate

120mg/6 ml contains 6 ml of concentrate. 

140mg/7 ml contains 7 ml of concentrate. 

160mg/8 ml contains 8 ml of concentrate. 

Pack size:

Each box contains 1 vial.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Taxespira is an antineoplastic agent and, as with other potentially toxic compounds, caution should be 
exercised when handling it and preparing Taxespira solutions. The use of gloves is recommended. 

If Taxespira concentrate or infusion solution should come into contact with skin, wash immediately 
and thoroughly with soap and water. If Taxespira concentrate should come into contact with mucous 
membranes, wash immediately and thoroughly with water. 

Preparation for the intravenous administration

Preparation of the infusion solution
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 20 mg/1 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 80 mg/4 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 120 mg/6 ml concentrate for solution for infusion, which 
contains only 1 vial).

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DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 140 mg/7 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 160 mg/8 ml concentrate for solution for infusion, which 
contains only 1 vial).

Taxespira concentrate for solution for infusion requires NO prior dilution with a solvent and is 
ready to add to the infusion solution.

Each vial is of single use and should be used immediately. 

If the vials are stored under refrigeration, allow the required number of boxes of Taxespira concentrate 
for solution for infusion to stand below 25°C for 5 minutes before use. 

More than one vial of Taxespira concentrate for solution for infusion may be necessary to obtain the 
required dose for the patient. Aseptically withdraw the required amount of Taxespira concentrate for 
solution for infusion using a calibrated syringe fitted with a 21G needle.

In Taxespira 20 mg/1 ml, 80 mg/4 ml, 120 mg/6 ml, 140 mg/7 ml and 160 mg/8 ml vials the 
concentration of docetaxel is 20 mg/ml.

The required volume of Taxespira concentrate for solution for infusion must be injected via a single 
infusion (one shot) into a 250 ml infusion bag or bottle containing either 5% glucose solution or 
sodium chloride 9 mg/ml (0.9%) solution for infusion. 

If a dose greater than 190 mg of docetaxel is required, use a larger volume of the infusion vehicle so 
that a concentration of 0.74 mg/ml docetaxel is not exceeded. 

Mix the infusion bag or bottle manually using a rocking motion. 

The infusion bag solution should be used within 6 hours below 25°C including the one hour infusion 
to the patient. 

As with all parenteral products, docetaxel 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

Hospira UK Limited
Horizon,
Honey Lane,
Hurley,
Maidenhead,
SL6 6RJ,

United Kingdom

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8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/001
EU/1/15/1017/002
EU/1/15/1017/003
EU/1/15/1017/004
EU/1/15/1017/005

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28 August 2015

10. DATE OF REVISION OF THE TEXT

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

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ANNEX II

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 
ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT

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A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release
Hospira UK Limited
Horizon,
Honey Lane,
Hurley,
Maidenhead,
SL6 6RJ,
United Kingdom

Hospira Enterprises B.V.
Randstad 22-11
NL-1316 BN Almere
The Netherlands

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 Periodic safety update reports 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.
An updated RMP should be submitted:

 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

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

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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

Taxespira 20 mg/1 ml concentrate for solution for infusion.
Docetaxel

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 1 ml of concentrate contains 20 mg docetaxel (as trihydrate). 

3. LIST OF EXCIPIENTS

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), citric acid 
monohydrate. 

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion.

1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use.

Ready to add to infusion solution.

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Cytotoxic

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8. EXPIRY DATE

Exp: 

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

Single use vials.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Hurley,
SL6 6RJ,
United Kingdom

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/001 20 mg/1 ml vial x 1 vial

13. BATCH NUMBER

Lot: 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

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18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
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NN: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Outer Carton 

1. NAME OF THE MEDICINAL PRODUCT

Taxespira 80 mg/4 ml concentrate for solution for infusion.
Docetaxel

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 1 ml of concentrate contains 20 mg docetaxel (as trihydrate). 

3. LIST OF EXCIPIENTS

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), citric acid 
monohydrate.

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion.

1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use

Ready to add to infusion solution.

Read the package leaflet before use

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Cytotoxic

8. EXPIRY DATE

Exp: 

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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

Single use vials.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Hurley,
SL6 6RJ,
United Kingdom

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/002 80 mg/4 ml vial x 1 vial

13. BATCH NUMBER

Lot: 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Outer Carton 

1. NAME OF THE MEDICINAL PRODUCT

Taxespira 120 mg/6 ml concentrate for solution for infusion.
Docetaxel

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 1 ml of concentrate contains 20 mg docetaxel (as trihydrate). 

3. LIST OF EXCIPIENTS

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), citric acid 
monohydrate. 

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion.

1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use.

Ready to add to infusion solution.

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Cytotoxic

8. EXPIRY DATE

Exp: 

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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

Single use vials.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Hurley,
SL6 6RJ,
United Kingdom

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/003 120 mg/6 ml vial x 1 vial

13. BATCH NUMBER

Lot: 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Outer Carton 

1. NAME OF THE MEDICINAL PRODUCT

Taxespira 140 mg/7 ml concentrate for solution for infusion.
Docetaxel

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 1 ml of concentrate contains 20 mg docetaxel (as trihydrate).

3. LIST OF EXCIPIENTS

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), citric acid 
monohydrate.

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion.

1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use.

Ready to add to infusion solution.

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Cytotoxic

8. EXPIRY DATE

Exp: 

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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

Single use vials.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Hurley,
SL6 6RJ,
United Kingdom

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/004 140 mg/7 ml vial x 1 vial

13. BATCH NUMBER

Lot: 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Outer Carton 

1. NAME OF THE MEDICINAL PRODUCT

Taxespira 160 mg/8 ml concentrate for solution for infusion.
Docetaxel

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each 1 ml of concentrate contains 20 mg docetaxel (as trihydrate). 

3. LIST OF EXCIPIENTS

Excipients: polysorbate 80, ethanol anhydrous (see leaflet for further information), citric acid 
monohydrate. 

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion.

1 vial

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use.

Ready to add to infusion solution.

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Cytotoxic

8. EXPIRY DATE

Exp: 

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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

Single use vials.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Hurley,
SL6 6RJ,
United Kingdom

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1017/005 160 mg/8 ml vial x 1 vial

13. BATCH NUMBER

Lot: 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 

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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

Taxespira 20 mg/1 ml concentrate for solution for infusion.
Docetaxel 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Lot: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

20 mg/1 ml 

(20mg/ml)

6. OTHER

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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

Taxespira 80 mg/4 ml concentrate for solution for infusion.
Docetaxel 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Lot: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

80 mg/4 ml

(20mg/ml)

6. OTHER

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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

Taxespira 120 mg/6 ml concentrate for solution for infusion.
Docetaxel 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Lot: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

120 mg/6 ml

(20mg/ml)

6. OTHER

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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

Taxespira 140 mg/7 ml concentrate for solution for infusion.
Docetaxel 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Lot: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

140 mg/7 ml

(20mg/ml)

6. OTHER

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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

Taxespira 160 mg/8 ml concentrate for solution for infusion.
Docetaxel 
IV

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

Lot: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

160 mg/8 ml

(20mg/ml)

6. OTHER

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B. PACKAGE LEAFLET

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Package leaflet: Information for the patient 

Taxespira 20 mg/1 ml concentrate for solution for infusion
Taxespira 80 mg/4 ml concentrate for solution for infusion

Taxespira 120 mg/6 ml concentrate for solution for infusion
Taxespira 140 mg/7 ml concentrate for solution for infusion
Taxespira 160 mg/8 ml concentrate for solution for infusion

Docetaxel

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, hospital pharmacist or nurse.
 If you get any side effects talk to your doctor, hospital pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Taxespira is and what it is used for
2. What you need to know before you use Taxespira
3. How to use Taxespira
4. Possible side effects
5. How to store Taxespira
6. Contents of the pack and other information

1. What Taxespira is and what it is used for

The name of this medicine is Taxespira. Its common name is docetaxel. Docetaxel is a substance 
derived from the needles of yew trees. Docetaxel belongs to the group of anti-cancer medicines called 
taxoids.

Taxespira 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, Taxespira 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, Taxespira

could be administered in combination with doxorubicin and cyclophosphamide.
 For the treatment of lung cancer, Taxespira could be administered either alone or in 

combination with cisplatin.
 For the treatment of prostate cancer, Taxespira is administered in combination with prednisone 

or prednisolone.
 For the treatment of metastatic gastric cancer, Taxespira is administered in combination with 

cisplatin and 5-fluorouracil.
 For the treatment of head and neck cancer, Taxespira is administered in combination with 

cisplatin and 5-fluorouracil.

2. What you need to know before you use Taxespira

You must not be given Taxespira

 if you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Taxespira
(listed in section 6).

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

Warnings and precautions 

Before each treatment with Taxespira, you will have blood tests to check that you have enough blood 
cells and sufficient liver function to receive Taxespira. In case of white blood cells disturbances, you 
may experience associated fever or infections.

Tell your doctor, hospital pharmacist, or nurse immediately if you have abdominal pain or tenderness, 
diarrhoea, rectal haemorrhage, blood in stool or fever. These symptoms may be the first signs of a 
serious gastrointestinal toxicity, which could be fatal. Your doctor should address them immediately.

Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision problems, 
in particular blurred vision, you should immediately have your eyes and vision examined.

Tell your doctor, hospital pharmacist or nurse if you have heart problems.
Tell your doctor, hospital pharmacist or nurse if you have experienced an allergic reaction to previous 
paclitaxel therapy.

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 Taxespira 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 Taxespira 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.

Taxespira contains alcohol. Discuss with your doctor if you suffer from alcohol dependency, epilepsy,
or liver impairment. See also section “Taxespira contains ethanol (alcohol)” below.

Other medicines and Taxespira

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 Taxespira or the other
medicine may not work as well as expected and you may be more likely to get a side effect.
The amount of alcohol in this medicinal product may alter the effects of other medicines.

Pregnancy, breast-feeding and fertility

Ask your doctor for advice before being given any medicine.

Taxespira 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 Taxespira 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 Taxespira.

If you are a man being treated with Taxespira 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.

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Driving and using machines

The amount of alcohol in this medicinal product may impair your ability to drive or use machines.
You may experience side effects of this medicine that may impair your ability to drive, use tools or 
operate machines (see section 4 Possible side effects). If this happens, do not drive or use any tools or 
machines before discussing with your doctor, nurse or hospital pharmacist.

Taxespira contains ethanol (alcohol)

20mg/1ml:
This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 395 mg ethanol anhydrous per 
1 ml, equivalent to 10 ml of beer or 4 ml wine.

80mg/4 ml: 
This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 1580 mg ethanol anyhdrous 
per 4 ml vial, equivalent to 40 ml of beer or 17 ml wine.

120mg/6 ml: 
This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2370 mg ethanol anhydrous 
per 6 ml vial, equivalent to 60 ml of beer or 25 ml wine.

140mg/7 ml: 
This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 2765 mg ethanol anhydrous 
per 7 ml vial, equivalent to 70 ml of beer or 29 ml wine.

160mg/8 ml: 
This medicine contains 50 vol % ethanol anhydrous (alcohol), i.e. up to 3160 mg ethanol anhydrous 
per 8 ml vial, equivalent to 80 ml of beer or 33 ml wine.

The amount of alcohol in this medicinal product may have effects on the central nervous system (the 
part of the nervous system that includes the brain and spinal cord).

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. 

3. How to use Taxespira

Taxespira 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

Taxespira 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.

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Your doctor may change the dose and frequency of dosing depending on your blood tests, your 
general condition and your response to Taxespira. 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 the 
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 Taxespira alone are: decrease in the number of red 
blood cells or white blood cells, alopecia (hair loss), nausea, vomiting, sores in the mouth, diarrhoea 
and tiredness.

The severity of adverse events of Taxespira may be increased when Taxespira is given in combination 
with other chemotherapeutic agents.

During the infusion at the hospital the following allergic reactions may occur (may affect more than 1 
in 10 people):
 flushing, skin reactions, itching
 chest tightness; difficulty in breathing
 fever or chills
 back pain
 low blood pressure.
More severe reactions may occur.
If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, 
which may be more severe.

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects.

Between infusions of Taxespira 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 blood cells (anaemia), or white blood cells (which are 

important in fighting infection) and platelets (important in blood clotting)
 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
 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

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 bleeding from the nose
 sores in the mouth
 stomach upsets including nausea, vomiting and diarrhoea, constipation
 abdominal pain
 indigestion
 hair loss: in most cases normal hair growth should return. In some cases (frequency not known) 

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

skin to peel (this may also occur on the arms, face, or body)
 change in the colour of your nails, which may detach
 muscle aches and pains; back pain or bone pain
 change or absence of menstrual periods
 swelling of the hands, feet, legs
 tiredness or flu-like symptoms
 weight gain or loss.

Common (may affect up to 1 in 10 people):
 oral candidiasis (thrush)
 dehydration
 dizziness
 hearing impaired
 decrease in blood pressure; irregular or rapid heart beat
 heart failure
 oesophagitis (inflammation of the gullet)
 dry mouth
 difficulty or painful swallowing
 haemorrhage (bleeding)
 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
 blood clots.

Rare (may affect up to 1 in 1,000 people):
• inflammation of the colon, small intestine, which could be fatal (frequency not known); 

intestinal perforation.

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

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy)
 pneumonia (infection of the lungs)
 pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath)
 blurred vision due to swelling of the retina within the eye (cystoid macular oedema)
 decrease of the sodium, potassium, magnesium, and/or calcium in your blood (electrolyte 

balance disorders).
 ventricular arrhythmia or ventricular tachycardia (manifested as irregular and/or rapid heartbeat, 

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

 injection site reactions at the site of a previous reaction.

Reporting of side effects
If you get any side effects talk to your doctor, hospital pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting

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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 Taxespira

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the outer carton and on the label of 
the vial after EXP. The expiry date refers to the last day of that month.

Do not store above 25°C.

Store in the original package in order to protect from light.

Use the vial immediately after its opening. If not used immediately, in-use storage times and 
conditions are the responsibility of the user.

From a microbiological point of view, reconstitution/dilution must take place in controlled and aseptic 
conditions.

Use immediately the medicine once added into the infusion bag. If not used immediately, in-use 
storage times and conditions are the responsibility of the user and would normally not be longer than 
6 hours below 25°C including the one hour infusion.

Physical and chemical in-use stability of the infusion solution prepared as recommended has been 
demonstrated in non-PVC bags up to 48 hours when stored between 2°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 Taxespira contains 

- The active substance is docetaxel (as trihydrate). Each ml of solution contains 20 mg of docetaxel (as 
trihydrate).

20mg/1 ml 
One vial of 1 ml of concentrate contains 20 mg docetaxel.

80mg/4 ml
One vial of 4 ml concentrate contains 80 mg docetaxel.

120mg/6 ml
One vial of 6 ml concentrate contains 120 mg docetaxel. 

140mg/7 ml
One vial of 7 ml concentrate contains 140 mg docetaxel. 

160mg/8 ml
One vial of 8 ml concentrate contains 160 mg docetaxel. 

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- The other ingredients are polysorbate 80, ethanol anhydrous (see section 2) and citric acid 
monohydrate.

What Taxespira looks like and contents of the pack

Taxespira concentrate for solution for infusion is a pale yellow to brownish-yellow solution provided 
in glass vials. 

Vials containing 20 mg/1 ml, 80 mg/4 ml, 120 mg/6 ml, 140 mg/7 ml and 160 mg/8 ml are available in 
packs containing a single vial.

Not all pack sizes are marketed. 

Marketing Authorisation Holder and Manufacturer

Hospira UK Limited
Horizon,
Honey Lane,
Hurley,
Maidenhead,
SL6 6RJ,
United Kingdom

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

BE / LU
Pfizer SA/NV
Tél/Tel: +32 2 554 62 11

LV
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

BG / EL / MT / RO / UK
Hospira UK Limited
Tel: + 44 (0) 1628 515500

LT
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

CZ
Pfizer, spol. s r.o.
Tel: +420-283-004-111

HU
Pfizer Kft.
Tel: + 36 1 488 37 00

DK
Pfizer ApS
Tlf: + 45 44 20 11 00

NL 
Pfizer bv
Tel: +31 (0)10 406 43 01

DE 
Pfizer Pharma PFE GmbH
Tel: + 49 (0)800 8535555

NO
Pfizer AS
Tlf: +47 67 52 61 00

EE
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

AT 
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

ES
Pfizer GEP, S.L.
Tel: +34 91 490 99 00

PL
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

FR PT

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Pfizer PFE France
Tél: + 33 (0)1 58 07 34 40

Laboratórios Pfizer, Lda.
Tel:  +351 21 423 55 00

HR
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

SI
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IE
Hospira Ireland Sales Limited
Tel: 1800 633 363 (toll free) 
+44 (0) 1304 616161

SK
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421–2–3355 5500

IS
Icepharma hf.
Sími: +354 540 8000

FI
Pfizer PFE Finland Oy
Puh/Tel: +358 (0)9 430 040

IT
Pfizer Italia Srl
Tel: +39 06 33 18 21

SE
Pfizer AB
Tel: +46 (0)8 550 520 00

CY 
Pharmaceutical Trading Co Ltd
Τηλ: 24656165

This leaflet was last revised in {month YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 

------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

PREPARATION GUIDE FOR USE WITH TAXESPIRA CONCENTRATE FOR SOLUTION 
FOR INFUSION

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

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Preparation of the infusion solution
DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 20 mg/1 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 80 mg/4 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 120 mg/6 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 140 mg/7 ml concentrate for solution for infusion, which 
contains only 1 vial).

DO NOT use other docetaxel medicinal products consisting of 2 vials (concentrate and solvent) 
with this medicinal product (Taxespira 160 mg/8 ml concentrate for solution for infusion, which 
contains only 1 vial).

Taxespira concentrate for solution for infusion requires NO prior dilution with a solvent and is 
ready to add to the infusion solution.
 Each vial is for single use and should be used immediately after opening. If not used 

immediately, in-use storage times and conditions are the responsibility of the user. More than 
one vial of Taxespira 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 
Taxespira 20 mg/1 ml concentrate for solution for infusion.

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

In Taxespira 20 mg/1 ml, 80 mg/4 ml, 120 mg/6 ml, 140 mg/7 ml and 160 mg/8 ml vials the 
concentration of docetaxel is 20 mg/ml.

 Inject the required dose (in mg) via a single injection (one shot) into a 250 ml non-PVC 
infusion bag containing either 5% glucose solution or sodium chloride 9 mg/ml (0.9%) 
solution for infusion or with 5% glucose solution in a glass bottle. If a dose greater than 
190 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a 
concentration of 0.74 mg/ml docetaxel is not exceeded.

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

and aseptic conditions and the infusion solution should be used immediately. If not used 
immediately, in-use storage times and conditions are the responsibility of the user.
Once added as recommended into the infusion bag, the docetaxel infusion solution, if stored 
below 25°C, is stable for 6 hours. It should be used within 6 hours (including the one hour 
infusion intravenous administration).
In addition, physical and chemical in-use stability of the infusion solution prepared as
recommended in non-PVC bags or bottles has been demonstrated up to 48 hours when stored 
between 2°C to 8°C, and for up to 6 hours when stored below 25°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

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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. These measures will help 
protect the environment.

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	ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET