Docetaxel Teva Pharma

1

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva Pharma 20 mg concentrate and solvent for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single-dose vial of Docetaxel Teva Pharma concentrate contains 20 mg docetaxel (anhydrous). 
Each ml of concentrate contains 27.73 mg docetaxel. 
 
Excipients with known effect:  
Each vial of concentrate contains 25.1% (w/w) anhydrous ethanol. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 

Concentrate and solvent for solution for infusion. 
The concentrate is a clear viscous, yellow to brown-yellow solution. 
The solvent is a colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Teva Pharma 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. 
 
Non-small cell lung cancer 
 
Docetaxel Teva Pharma is indicated for the treatment of patients with locally advanced or metastatic 
non-small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Teva Pharma in combination with cisplatin is indicated for the treatment of patients with 
unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 
previously received chemotherapy for this condition. 
 
Prostate cancer 
 
Docetaxel Teva Pharma in combination with prednisone or prednisolone is indicated for the treatment 
of patients with hormone refractory metastatic prostate cancer. 
 
4.2 Posology and method of administration 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 
chemotherapy and it should only be administered under the supervision of a physician qualified in the 
use of anticancer chemotherapy (see section 6.6). 
 
Recommended dose 
 
For breast and non-small cell lung cancer, 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 

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administration, unless contraindicated, can be used (see section 4.4). Prophylactic G-CSF may be used 
to mitigate the risk of haematological toxicities. 
 
For prostate cancer, given the concurrent use of prednisone or prednisolone the recommended 
premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel 
infusion (see section 4.4).  
 
Docetaxel is administered as a one-hour infusion every three weeks. 
 
Breast cancer 
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy.  
 
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). 
 
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. 
 
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 characeteristics. 
 
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. 
 
Paediatric population 
The safety and efficacy of Docetaxel Teva Pharma in nasopharyngeal carcinoma in children aged 
1 month to less than 18 years have not yet been established. 
There is no relevant use of Docetaxel Teva Pharma in the paediatric population in the indications 
breast cancer, non-small cell lung cancer and prostate cancer. 
 
Older People 

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Based on a population pharmacokinetic analysis, there are no special instructions for use in older 
people. 
 
4.3 Contraindications 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Docetaxel must not be used in patients with baseline neutrophil count of <1,500 cells/mm3. 
 
Docetaxel must not be used in patients with severe liver impairment since there is no data available 
(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). 
 
Hypersensitivity reactions 
 
Patients should be observed closely for hypersensitivity reactions especially during the first and 
second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 
of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. 
 
Cutaneous reactions 

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

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treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 
more details see Summary of Product Characteristics of trastuzumab. 
 
Eye disorders 
 
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel.  Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examination.  In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatment initiated (see section 
4.8). 
 
Others 
 
Contraceptive measures must be taken by both men and women during treatment and for men at least 
6 months after cessation of therapy (see section 4.6). 
 
Additional cautions for use in adjuvant treatment of breast cancer 
Complicated neutropenia 
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 
 
Gastrointestinal reactions 
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 
 
Congestive heart failure (CHF) 
Patients should be monitored for symptoms of congestive heart failure during therapy and during the 
follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of 
CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 
 
Leukaemia 
In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 
 
Patients with 4+ nodes 
As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 
nodes was not fully demonstrated at the final analysis (see section 5.1). 
 
Older people 
There are limited 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. 

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Older people treated with TCF should be closely monitored. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as cyclosporine, terfenadine, ketoconazole, 
erythromycin and troleandomycin. 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. 
 
Docetaxel is highly protein bound (>95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal products has not been investigated formally, in vitro 
interactions with tightly protein-bound drugs 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 
coadministration. 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. 
 
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. 
 
Clinical cases consistent with an increase in docetaxel toxicity were reported when it was combined 
with ritonavir.  The mechanism behind this interaction is a CYP3A4 inhibition, the main isoenzyme 
involved in docetaxel metabolism by ritonavir.  Based on extrapolation from a pharmacokinetic study 
with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require co-
administrtion of a stron CYP3A4 inhibitor such as azole antifungals, ritonavir and some macrolides 
(clarithromycin, telithromycin). 
 
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. 
 
Contracteption in males and females 
 
An effective method of contraception should be used during treatment. 
 
Fertility 
 

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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. 
 
4.8 Undesirable effects 
 
Summary of the safety profile for all indications 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in: 
• 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 

respectively. 
• 258 patients who received docetaxel in combination with doxorubicin. 
• 406 patients who received docetaxel in combination with cisplatin. 
• 92 patients treated with docetaxel in combination with trastuzumab. 
• 255 patients who received docetaxel in combination with capecitabine. 
• 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically 

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

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

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

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

 
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 
grade 3-4 = G3/4; grade 4 = G4) and 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 the available 
data). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 
reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 
neutropenia (<500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 
and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 
combination with other chemotherapeutic agents. 
 
For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 
was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 
trastuzumab combination arm compared to docetaxel monotherapy. 
 
For combination with capecitabine, the most frequent treatment-related undesirable effects (≥ 5%) 
reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 
capecitabine summary of product characteristics). 
 
The following adverse reactions are frequently observed with docetaxel: 
 

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Immune system disorders 
 
Hypersensitivity reactions have generally occurred within a few minutes following the start of the 
infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 
were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills.  
Severe reactions were characterised by hypotension and/or bronchospasm or generalized 
rash/erythema (see section 4.4). 
 
Nervous system disorders 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 
and 4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain 
including burning. Neuro-motor events are mainly characterised by weakness. 
 
Skin and subcutaneous tissue disorders 
 
Reversible cutaneous reactions have been observed and were generally considered as mild to 
moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 
hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 
associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 
Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 
interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 
nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 
 
General disorders and administration site conditions 
 
Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 
redness or dryness of the skin, phlebitis or extravasations and swelling of the vein. 
Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 
pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 
extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 
cumulative in incidence and severity (see section 4.4). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 100 mg/m² single agent 
MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  

Infections and 
infestations 

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

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

 

Blood and lymphatic 
system disorders 

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

Thrombocytopenia 
(G4: 0.2%) 

 

Immune system 
disorders 

Hypersensitivity 
(G3/4: 5.3%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders  

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

  

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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, 
connective tissue 
disorders 

Myalgia (severe 1.4%) Arthralgia  

General disorders and 
administration site 
conditions 

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

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

 

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

 

 
Description of selected adverse reactions in breast cancer for Docetaxel 100 mg/m2 single agent 
 
Blood and lymphatic system disorders 
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia. 
 
Nervous system disorders 
Reversibility data are available among 35.3% of patients who developed neurotoxicity following 
docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 
3 months. 
 
Skin and subcutaneous tissue disorders 
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 
were reversible within 21 days. 
 
General disorders and administration site conditions 

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The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 
time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 
severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 
compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 
has been reported in some patients during the early courses of therapy. 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 75 mg/m² single agent 

MedDRA system srgan classes  Very common adverse 
reactions 

Common adverse reactions 
 

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

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

Febrile neutropenia 

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

Anorexia  

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

Peripheral motor neuropathy 
(G3/4: 2.5%) 

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

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

Constipation 

Skin and subcutaneous tissue 
disorders 

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

Nail disorders (severe 0.8%) 

Musculoskeletal and connective 
tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

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

 

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

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

Very common 
adverse reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

Infection (G3/4: 7.8%)   

Blood and lymphatic 
system disorders 

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

  

Immune system 
disorders 

 Hypersensitivity 
(G3/4: 1.2%) 

 

Metabolism and 
nutrition disorders 

 Anorexia  

Nervous system 
disorders  

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy 
(G3/4: 0.4%) 

 

Cardiac disorders  Cardiac failure;   

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Arrhythmia (no severe) 
Vascular disorders   Hypotension 
Gastrointestinal 
disorders  

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

  

Skin and subcutaneous 
tissue disorders 

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

  

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  

General disorders and 
administration site 
conditions 

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

Infusion site reaction  

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

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

 
Tabulated lit of adverse reactions in breast cancer for Docetaxel 75 mg/m² in combination with 
cisplatin 
 
MedDRA system 
organ classes 

Very common adverse 
reactions  

Common adverse 
reactions 

Uncommon adverse 
reactions 

Infections and 
infestations 

Infection (G3/4: 5.7%)   

Blood and lymphatic 
system disorders 

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

Febrile neutropenia 
 

 

Immune system 
disorders 

Hypersensitivity 
(G3/4: 2.5%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders  

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

  

Cardiac disorders  Arrhythmia 
(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders  Hypotension 
(G3/4: 0.7%) 

 

Gastrointestinal 
disorders  

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

Constipation  

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Stomatitis (G3/4: 2%) 
Skin and 
subcutaneous tissue 
disorders 

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

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 0.5%)  
 

 

General disorders 
and administration 
site conditions 

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

Infusion site reaction; 
Pain 

 

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

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

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

 
Common adverse 
reactions  
 

Blood and lymphatic system 
disorders  

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

 

Metabolism and nutrition 
disorders 

Anorexia  

Psychiatric disorders Insomnia  
Nervous system disorders  
 

Paresthesia; Headache; Dysgeusia; 
Hypoaesthesia 

 

Eye disorders  
 

Lacrimation increased; 
Conjunctivitis 

 

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

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

 

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

 

Skin and subcutaneous tissue 
disorders  

Alopecia; Erythema; Rash; Nail 
disorders 

 

Musculoskeletal and connective 
tissue disorders 

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

 

General disorders and 
administration site conditions 

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

Lethargy 

Investigations Weight increased  
 

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Description of selected adverse reactions in breast cancer for Docetaxel 100 mg/m2 in combination 
with trastuzumab 
 
Cardiac disorders 
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 
trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 
64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 
alone. 
 
Blood and lymphatic system disorders 
Very common: Haematological toxicity was increased in patients receiving trastuzumab and 
docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 
criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 
known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 
incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 
Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 75 mg/m² in combination with 
capecitabine 
 
MedDRA system organ 
classes  

Very common adverse 
reactions  

Common adverse reactions 
 

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

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

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

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

Dehydration (G3/4: 2%) 

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

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

Very common adverse 
reactions 

Common adverse reactions 
 

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

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

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

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

Anorexia (G3/4: 0.6%)  

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

Peripheral motor neuropathy 
(G3/4: 0%) 

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

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

Respiratory, thoracic and 
mediastinal disorders 

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

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

 

Skin and subcutaneous tissue 
disorders  
 

Alopecia; 
Nail disorders (no severe) 

Exfoliative rash (G3/4: 0.3%) 

Musculoskeletal and connective 
tissue 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 for adjuvant therapy with Docetaxel 75 mg/m² in combination with 
doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and node-negative 
(GEICAM 9805) breast cancer - pooled data 
 
MedDRA system 
organ classes 

Very common adverse 
reactions  

Common adverse 
reactions 

Uncommon adverse 
reactions 

Infections and 
infestations 

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

  

Blood and lymphatic 
system disorders 

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

  

Immune system 
disorders 

 Hypersensitivity 
(G3/4: 0.6%) 

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 1.5%)   

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MedDRA system 
organ classes 

Very common adverse 
reactions  

Common adverse 
reactions 

Uncommon adverse 
reactions 

Nervous system 
disorders  

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

Peripheral motor 
neuropathy 
(G3/4: 0%) 
 

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

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

Lacrimation increased 
(G3/4: <0.1%) 
 

 

Cardiac disorders  Arrhythmia 
(G3/4: 0.2%) 
 

 

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

Lymphoedema 
(G3/4: 0%) 

Respiratory, thoracic 
and mediastinal 
disorders 

 Cough (G3/4: 0%)  

Gastrointestinal 
disorders  

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

Abdominal pain 
(G3/4: 0.4%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia(G3/4: <0.1%); 
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 Docetaxel 75 mg/m2 in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316 and 
node-negative (GEICAM 9805) breast cancer 
 
Nervous system disorders 

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Peripheral sensory neuropathy was observed to be ongoing during follow-up in 10 patients out of the 
84 patients with peripheral sensory neuropathy at the end of the chemotherapy in the node positive 
breast cancer study (TAX316). 
 
Cardiac disorders 
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure.  All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period.  Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
 
Skin and subcutaneous tissue disorders 
In study TAX316, alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 TAC patients and 645 FAC patients. 
At the end of the follow-up period, alopecia was observed to be ongoing in 29 TAC patients (4.2%) 
and 16 FAC patients (2.4%). 
 
Reproductive system and breast disorders 
Amenorrhoea was observed to be ongoing during follow-up in 121 patients out of the 202 patients 
with amenorrhoea at the end of the chemotherapy in study TAX316. 
 
General disorders and administration site conditions 
In study TAX316, peripheral oedema was observed to be ongoing in 19 patients out of the 119 patients 
with peripheral oedema in the TAC arm and 4 patients out of the 23 patients with peripheral oedema in 
the FAC arm. 
In study GEICAM 9805, lymphoedema was observed to be ongoing in 4 of the 5 patients with 
lymphoedema at the end of the chemotherapy. 
 
Acute leukaemia / Myelodysplastic syndrome. 
After 10 years of follow up in study TAX316, acute leukaemia was reported in 4 of 744 TAC patients 
and in 1 of 736 FAC patients.  Myelodysplastic syndrome was reported in 2 of 744 TAC patients and 
in 1 of 736 FAC patients. 
At a median follow-up time of 77 months, acute leukaemia occurred in 1 of 532 (0.2%) patients who 
received docetaxel, doxorubicin, and cyclophosphamide in the GEICAM 9805 study. No cases were 
reported in patients who received fluorouracil, doxorubicin and cyclophosphamide. No patient was 
diagnosed with myelodysplastic syndrome in either treatment groups. 
 
Neutropenic complications 
Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 
infection was decreased in patients who received primary G-CSF prophylaxis after it was made 
mandatory in the TAC arm - GEICAM study. 
 
Neutropenic complications in patients receiving TAC with or without primary G-CSF prophylaxis 
(GEICAM 9805) 
 
 Without primary 

G-CSF prophylaxis 
(n = 111) 

n (%) 
 

With primary 
G-CSF prophylaxis 

(n = 421) 
n (%) 

 
Neutropenia (Grade 4) 104 (93.7) 135 (32.1) 
Febrile neutropenia 28 (25.2) 23 (5.5) 
Neutropenic infection 14 (12.6) 21 (5.0) 
Neutropenic infection 
(Grade 3-4) 

2 (1.8) 5 (1.2) 

 
Tabulated list of adverse reactions in gastric adenocarcinoma cancer for Docetaxel 75 mg/m² in 
combination with cisplatin and 5-fluorouracil 

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

MedDRA system 
organ classes  

Very common 
adverse reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

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

  

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

 Cancer pain 
(G3/4: 0.6%) 

 

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Blood and lymphatic 
system disorders 

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

Febrile neutropenia 

 

Immune system 
disorders 

 Hypersensitivity 
(no severe) 

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 0.6%)   

Nervous system 
disorders 

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

Dizziness 

 

Eye disorders  Lacrimation increased; Conjunctivitis 
 

Ear and labyrinth 
disorders  Hearing impaired  

 

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

Arrhythmia 
(G3/4: 0.6%) 

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

 

Gastrointestinal 
disorders  

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

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

 

Skin and subcutaneous 
tissue disorders  

Alopecia 
(G3/4: 10.9%) 

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

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.6%) 
 

General disorders and 
administration site 
conditions 

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

 

 

Investigations  Weight increased  
 

• 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 

  

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

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 12.0%)   

Nervous system 
disorders 

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

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

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia 
(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders   Venous disorder 
Gastrointestinal 
disorders  

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

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

 

Skin and subcutaneous 
tissue disorders  

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

Dry skin; 
Desquamation 

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.4%)  

General disorders and 
administration site 
conditions 

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

  

Investigations Weight decreased  Weight increased 
 
Post-marketing experience 
 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 
Cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association 
with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy. 
 
Blood and lymphatic system disorders 
Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been 
reported. 
 
Immune system disorders 
Some cases of anaphylactic shock, sometimes fatal, have been reported. 
 
Nervous system disorders 

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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 lachrymal 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. 
 
Vascular disorders 
Venous thromboembolic events have rarely been reported. 
 
Respiratory, thoracic and mediastinal disorders 
Acute respiratory distress syndrome and cases of interstitial pneumonia/pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 
 
Gastrointestinal disorders 
Rare occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal 
perforation, colitis ischaemic, colitis and neutropenic enterocolitis have been reported. Rare cases of 
ileus and intestinal obstruction have been reported. 
 
Hepatobiliary disorders 
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 
 
Skin and subcutaneous tissue disorders 
Very rare cases of cutaneous lupus erythematous and bullous eruptions such as erythema multiform, 
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 lymphedema have been reported with docetaxel.  Cases of 
persisting alopecia have been reported. 
 
Renal and urinary disorders 
Renal insufficiency and renal failure have been reported.  In about 20% of these cases there were no 
risk factors for acute renal failure concomitant nephrotoxic medicinal products and gastro-intestinal 
disorders. 
 
General disorders and administration site conditions 
Radiation recall phenomena have rarely been reported. 
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 
 
Metabolism and nutrition disorders 
Cases of hyponatraemia have been reported, mostly associated with dehydration, vomiting and 
pneumonia. 
 
Reporting of suspected adverse reactions 

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

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Taxanes, ATC Code: L01CD 02 
 
Mechanism of action 
 
Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 
microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 
binding of docetaxel to microtubules does not alter the number of protofilaments. 
 
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 
vital mitotic and interphase cellular functions. 
 
Pharmacodynamic effects 
 
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 
against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 
concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 
but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 
gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour 
activity against advanced murine and human grafted tumours. 
 
Clinical efficacy and safety 
 
Breast cancer 
Two randomised phase III comparative studies, involving a total of 326 alkylating or 
392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 
recommended dose and regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p=0.38) or 
time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p=0.54), docetaxel increased 
response rate (52% vs. 37%, p=0.01) and shortened time to response (12 weeks vs. 23 weeks, 
p=0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 15 
doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 
failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 
(33% vs. 12%, p<0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p=0.0004) and 
prolonged overall survival (11 months vs. 9 months, p=0.01). 

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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%). 
 
Non-small cell lung cancer 
 
Patients previously treated with chemotherapy with or without radiotherapy 
 
In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 
and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 
Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 
There was less use of morphinic analgesic (p<0.01), non-morphinic analgesics (p<0.01), other disease 
related medications (p=0.06) and radiotherapy (p<0.01) in patients treated with docetaxel at 75 mg/m² 
compared to those with BSC. 
The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 
26.1 weeks. 
 
Docetaxel in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
docetaxel (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml. min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 
administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 
day 1 of cycles repeated every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated 
in the following table: 
 
 TCis 

n=408 
 

VCis 
n=404 

 

Statistical Analysis 

Overall survival 
(Primary end-point): 

   

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

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

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

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

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

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[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 overall survival 
compared to those treated with mitoxantrone. The increase in survival seen in the docetaxel weekly 
arm was not statistically significant compared to the mitoxantrone control arm. Efficacy endpoints for 
the docetaxel arms versus the control arm are summarized in the following table: 
 
Endpoint 
 

Docetaxel 
every 3 weeks 

 

Docetaxel 
every week 

 

Mitoxantrone 
every 3 weeks 

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

335 
18.9 

(17.0-21.2) 
0.761 

(0.619-0.936) 
0.0094 

334 
17.4 

(15.7-19.0) 
0.912 

(0.747-1.113) 
0.3624 

337 
16.5 

(14.4-18.6) 
-- 
-- 
-- 

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

291 
45.4 

(39.5-51.3) 
0.0005 

282 
47.9 

(41.9-53.9) 
<0.0001 

300 
31.7 

(26.4-37.3) 
-- 

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

153 
34.6 

(27.1-42.7) 
0.0107 

154 
31.2 

(24.0-39.1) 
0.0798 

157 
21.7 

(15.5-28.9) 
-- 

Number of patients 
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. 

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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 coadministration. 
 
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 

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Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 
similar to that observed with cisplatin alone. 
 
Cisplatin and 5-fluorouracil 
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 
tumours had no influence on the pharmacokinetics of each individual medicinal product. 
 
Prednisone and dexamethasone 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 
dexamethasone premedication has been studied in 42 patients.  
 
Prednisone 
No effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
5.3 Preclinical safety data 
 
The carcinogenic potential of docetaxel has not been studied. 
 
Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 
test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 
mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 
with the pharmacological activity of docetaxel. 
 
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair 
male fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Concentrate  
Polysorbate 80 
Ethanol, anhydrous 
 
Solvent  
Water for injections. 
 
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 
 
• 18 months. 
• Premix solution: Chemical and physical in-use stability has been demonstrated for 8 hours when 

stored either between 2°C and 8°C or at room temperature (below 25°C). From a 
microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would 
normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 

• Infusion solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 
room temperature (below 25°C). From a microbiological point of view, the product should be 
used immediately. If not used immediately, in-use storage times and conditions prior to use are 

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the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless 
dilution has taken place in controlled and validated aseptic conditions. 

 
6.4 Special precautions for storage and other handling 
 

Do not store above 25°C . 
Do not freeze. 
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 
 
Each carton contains: 
• One vial of concentrate and, 
• One vial of solvent 
 
• Docetaxel Teva Pharma 20 mg vial  

6 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 
 

This vial contains 0.72 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill volume: 
24.4 mg/0.88 ml). This fill volume has been established during the development of docetaxel to 
compensate for liquid loss during preparation of the premix due to foaming, adhesion to the 
walls of the vial and "dead-volume". This overfill ensures that after dilution with the entire 
contents of the accompanying solvent for docetaxel vial, there is a minimal extractable premix 
volume of 2 ml containing 10 mg/ml docetaxel which corresponds to the labelled amount of 
20 mg per vial. 

 
Solvent for Docetaxel Teva Pharma 20 mg vial 
6 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 
 
Solvent vial contains 1.28 ml of water for injections (fill volume: 1.71 ml). The addition of the 
entire contents of the solvent vial to the contents of the Docetaxel Teva Pharma 20 mg 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 
6.6 Special precautions for disposal and other handling 
 
Docetaxel Teva Pharma is an antineoplastic agent and, as with other potentially toxic compounds, 
caution should be exercised when handling it and preparing Docetaxel solutions. The use of gloves is 
recommended. 
 
If Docetaxel Teva Pharma concentrate, premix solution or infusion solution should come into contact 
with skin, wash immediately and thoroughly with soap and water. If Docetaxel concentrate, premix 
solution or infusion solution should come into contact with mucous membranes, wash immediately 
and thoroughly with water. 
 
Preparation for the intravenous administration 

a) Preparation of the Docetaxel Teva Pharma premix solution (10 mg docetaxel/ml) 

If the vials are stored under refrigeration, allow the required number of Docetaxel Teva Pharma boxes 
to stand at room temperature (below 25°C) for 5 minutes. 
 
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva Pharma vial by partially inverting the vial. 
 
Inject the entire contents of the syringe into the corresponding Docetaxel Teva Pharma vial. 
 

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Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do 
not shake. 
 
Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then check that 
the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of 
polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after preparation. 
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours 
when stored either between 2°C and 8°C or at room temperature (below 25°C). 
 
b) Preparation of the infusion solution 

More than one premix vial may be necessary to obtain the required dose for the patient. Based on the 
required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume 
containing 10 mg/ml docetaxel from the appropriate number of premix vials using graduated syringes 
fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix 
solution. 
 
Inject the required premix volume into a non-PVC 250 ml infusion bag containing either 5% glucose 
solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 200 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 Docetaxel Teva Pharma infusion solution should be used within 4 hours and should be aseptically 
administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 
 
As with all parenteral products, Docetaxel Teva Pharma premix solution and 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 

Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/10/662/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
21st January 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 

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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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1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva Pharma 80 mg concentrate and solvent for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each single dose vial of Docetaxel Teva Pharma concentrate contains 80 mg docetaxel (anhydrous). 
Each ml of concentrate contains 27.73 mg docetaxel. 
 
Excipients with known effect:  
Each vial of concentrate contains 25.1% (w/w) anhydrous ethanol. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 

Concentrate and solvent for solution for infusion. 
The concentrate is a clear viscous, yellow to brown-yellow solution. 
The solvent is a colourless solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Breast cancer 
 
Docetaxel Teva Pharma 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. 
 
Non-small cell lung cancer 
 
Docetaxel Teva Pharma is indicated for the treatment of patients with locally advanced or metastatic 
non-small cell lung cancer after failure of prior chemotherapy. 
 
Docetaxel Teva Pharma in combination with cisplatin is indicated for the treatment of patients with 
unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not 
previously received chemotherapy for this condition. 
 
Prostate cancer 
 
Docetaxel Teva Pharma in combination with prednisone or prednisolone is indicated for the treatment 
of patients with hormone refractory metastatic prostate cancer. 
 
4.2 Posology and method of administration 

The use of docetaxel should be confined to units specialised in the administration of cytotoxic 
chemotherapy and it should only be administered under the supervision of a physician qualified in the 
use of anticancer chemotherapy (see section 6.6). 
 
Recommended dose 
 
For breast and non-small cell lung cancer, 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 

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administration, unless contraindicated, can be used (see section 4.4). Prophylactic G-CSF may be used 
to mitigate the risk of haematological toxicities. 
 
For prostate cancer, given the concurrent use of prednisone or prednisolone the recommended 
premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel 
infusion (see section 4.4).  
 
Docetaxel is administered as a one-hour infusion every three weeks. 
 
Breast cancer 
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose 
of docetaxel is 100 mg/m2 in monotherapy.  
 
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). 
 
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. 
 
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 characeteristics. 
 
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. 
 
Paediatric population 
The safety and efficacy of Docetaxel Teva Pharma in nasopharyngeal carcinoma in children aged 
1 month to less than 18 years have not yet been established. 
There is no relevant use of Docetaxel Teva Pharma in the paediatric population in the indications 
breast cancer, non-small cell lung cancer and prostate cancer. 
 
Older people 

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Based on a population pharmacokinetic analysis, there are no special instructions for use in older 
people.  
 
4.3 Contraindications 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Docetaxel must not be used in patients with baseline neutrophil count of <1,500 cells/mm3. 
 
Docetaxel must not be used in patients with severe liver impairment since there is no data available 
(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). 
 
Hypersensitivity reactions 
 
Patients should be observed closely for hypersensitivity reactions especially during the first and 
second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation 
of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should 
be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised 
cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe 
hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of 
docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions 
should not be re-challenged with docetaxel. 
 
Cutaneous reactions 

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Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema 
followed by desquamation has been observed. Severe symptoms such as eruptions followed by 
desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see 
section 4.2). 
 
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, interstitital lung disease, 
pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal 
outcome.  Cases of radiation pneumonitis have been reported in patients receiving concomitant 
radiotherapy. 
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly 
investigated, and appropriately treated.  Interruption of docetaxel therapy is recommended until 
diagnosis is available.  Early use of supportive care measures may help improve the condition.  The 
benefit of resuming docetaxel treatment must be carefully evaluated. 
 
Patients with liver impairment 
 
In patients treated with docetaxel at 100 mg/m2 as single agent who have serum transaminase levels 
(ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels 
greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as 
toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, 
infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel 
in those patients with elevated liver function test (LFTs) is 75 mg/m2 and LFTs should be measured at 
baseline and before each cycle (see section 4.2). 
For patients with serum bilirubin levels >ULN and/or ALT and AST >3.5 times the ULN concurrent 
with serum alkaline phosphatase levels >6 times the ULN, no dose-reduction can be recommended 
and docetaxel should not be used unless strictly indicated. 
In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric 
adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN 
associated with alkaline phosphatase > 2.5 × ULN, and bilirubin> 1 x UNL; 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 

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treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For 
more details see Summary of Product Characteristics of trastuzumab. 
 
Eye disorders 
 
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel.  Patients with 
impaired vision should undergo a prompt and complete ophthalmologic examiniation.  In case CMO is 
diagnosed, docetaxel treatment should be discontinued and appropriate treatement 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). 
 
Additional cautions for use in adjuvant treatment of breast cancer 
Complicated neutropenia 
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or 
infection), G-CSF and dose reduction should be considered (see section 4.2). 
 
Gastrointestinal reactions 
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, 
may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated 
promptly. 
 
Congestive heart failure (CHF) 
Patients should be monitored for symptoms of congestive heart failure during therapy and during the 
follow up period.  In patients treated with the TAC regimen for node positive breast cancer, the risk of 
CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1). 
 
Leukaemia 
In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed 
myelodysplasia or myeloid leukaemia requires haematological follow-up. 
 
Patients with 4+ nodes 
As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free 
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ 
nodes was not fully demonstrated at the final analysis (see section 5.1). 
 
Older people 
There are limited 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. 

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Older people treated with TCF should be closely monitored. 
 
4.5 Interaction with other medicinal products and other forms of interaction 

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant 
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the 
enzyme competitively) cytochrome P450-3A such as cyclosporine, terfenadine, ketoconazole, 
erythromycin and troleandomycin. 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. 
 
Docetaxel is highly protein bound (>95%). Although the possible in vivo interaction of docetaxel with 
concomitantly administered medicinal products has not been investigated formally, in vitro 
interactions with tightly protein-bound drugs 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 
coadministration. 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. 
 
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. 
 
Clincal cases consistent with an increase in docetaxel toxicity were reported when it was combined 
with ritonavir.  The mechanism behind this interaction is a CYP3A4 inhibition, the main isoenzyme 
involved in docetaxel metabolism by ritonavir.  Based on extrapolation from a pharmacokinetic study 
with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require co-
administration of a strong CYP3A4 inhibitor such as azole antifungals, ritonavir and some macrolides 
(clarithromycin, telithromycin). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be 
both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other 
cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant 
women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.  
 
Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to 
inform the treating physician immediately should this occur. 
 
Breast-feeding 
 
Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. 
Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be 
discontinued for the duration of docetaxel therapy. 
 
Contraception in males and females 
 
An effective method of contraception should be used during treatment. 
 
Fertility 
 

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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. 
 
4.8 Undesirable effects 
 
Summary of the safety profile for all indications 
 
The adverse reactions considered to be possibly or probably related to the administration of docetaxel 
have been obtained in: 
• 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent 

respectively. 
• 258 patients who received docetaxel in combination with doxorubicin. 
• 406 patients who received docetaxel in combination with cisplatin. 
• 92 patients treated with docetaxel in combination with trastuzumab. 
• 255 patients who received docetaxel in combination with capecitabine. 
• 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically 

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

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

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

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

 
These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; 
grade 3-4 = G3/4; grade 4 = G4) and the COSTART and the MedRA 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 the available 
data). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was 
reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe 
neutropenia (<500 cells/mm3) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea 
and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in 
combination with other chemotherapeutic agents. 
 
For combination with trastuzumab, adverse events (all grades) reported in ≥ 10% are displayed. There 
was an increased incidence of SAEs (40% vs. 31%) and Grade 4 AEs (34% vs. 23%) in the 
trastuzumab combination arm compared to docetaxel monotherapy. 
 
For combination with capecitabine, the most frequent treatment-related undesirable effects  (≥ 5%) 
reported in a phase III study in breast cancer patients failing anthracycline treatment are presented (see 
capecitabine summary of product characteristics). 
 
The following adverse reactions are frequently observed with docetaxel: 
 

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Immune system disorders 
 
Hypersensitivity reactions have generally occurred within a few minutes following the start of the 
infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms 
were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills.  
Severe reactions were characterised by hypotension and/or bronchospasm or generalized 
rash/erythema (see section 4.4). 
 
Nervous system disorders 
 
The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 
and 4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain 
including burning. Neuro-motor events are mainly characterised by weakness. 
 
Skin and subcutaneous tissue disorders 
 
Reversible cutaneous reactions have been observed and were generally considered as mild to 
moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and 
hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently 
associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. 
Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to 
interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe 
nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis. 
 
General disorders and administration site conditions 
 
Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, 
redness or dryness of the skin, phlebitis or extravasations and swelling of the vein. 
Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, 
pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower 
extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is 
cumulative in incidence and severity (see section 4.4). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 100 mg/m² single agent 
MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  

Infections and 
infestations 

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

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

 

Blood and lymphatic 
system disorders 

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

Thrombocytopenia 
(G4: 0.2%) 

 

Immune system 
disorders 

Hypersensitivity (G3/4:  
5.3%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders  

Peripheral sensory 
neuropathy (G3: 4.1%);  

  

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MedDRA system 
organ classes  

Very common adverse 
reactions  

Common adverse 
reactions   

Uncommon adverse 
reactions  

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

Cardiac disorders  Arrhythmia 
(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders  Hypotension; 
Hypertension 
Haemorrhage 

 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea (severe 2.7%)   

Gastrointestinal 
disorders  

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

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

Oesophagitis 
(severe: 0.4%) 

Skin and subcutaneous 
tissue disorders 

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

  

Musculoskeletal, 
connective tissue 
disorders 

Myalgia (severe 1.4%) Arthralgia  

General disorders and 
administration site 
conditions 

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

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

 

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

 

 
Description of selected adverse reactions in breast cancer for Docetaxel 100 mg/m2 single agent 
 
Blood and lymphatic system disorders 
Rare: bleeding episodes associated with grade 3/4 thrombocytopenia. 
 
Nervous system disorders 
Reversibility data are available among 35.3% of patients who developed neurotoxicity following 
docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 
3 months. 
 
Skin and subcutaneous tissue disorders 
Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions 
were reversible within 21 days. 

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General disorders and administration site conditions 
The median cumulative dose to treatment discontinuation was more than 1,000 mg/m2 and the median 
time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and 
severe retention is delayed (median cumulative dose: 818.9 mg/m2) in patients with premedication 
compared with patients without premedication (median cumulative dose: 489.7 mg/m2); however, it 
has been reported in some patients during the early courses of therapy. 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 75 mg/m² single agent 

MedDRA system organ 
classes  

Very common adverse 
reactions 

Common adverse reactions 
 

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

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

Febrile neutropenia 

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

Anorexia  

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

Peripheral motor neuropathy 
(G3/4: 2.5%) 

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

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

Constipation 

Skin and subcutaneous tissue 
disorders 

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

Nail disorders (severe 0.8%) 

Musculoskeletal and connective 
tissue disorders 

 Myalgia 

General disorders and 
administration site conditions 

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

 

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

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

Very common 
adverse reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

Infections and 
infestations 

Infection (G3/4: 7.8%)   

Blood and lymphatic 
system disorders 

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

  

Immune system 
disorders 

 Hypersensitivity 
(G3/4: 1.2%) 

 

Metabolism and 
nutrition disorders 

 Anorexia  

Nervous system 
disorders  

Peripheral sensory 
neuropathy (G3: 0.4%) 

Peripheral motor 
neuropathy 
(G3/4: 0.4%) 

 

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Cardiac disorders  Cardiac failure;  
Arrhythmia (no severe) 

 

Vascular disorders   Hypotension 
Gastrointestinal 
disorders  

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

  

Skin and subcutaneous 
tissue disorders 

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

  

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia  

General disorders and 
administration site 
conditions 

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

Infusion site reaction  

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

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

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

Very common adverse 
reactions 

Common adverse 
reactions 

Uncommon adverse 
reactions 

Infections and 
infestations 

Infection (G3/4: 5.7%)   

Blood and lymphatic 
system disorders 

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

Febrile neutropenia 
 

 

Immune system 
disorders 

Hypersensitivity 
(G3/4: 2.5%) 

  

Metabolism and 
nutrition disorders 

Anorexia   

Nervous system 
disorders  

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

  

Cardiac disorders  Arrhythmia 
(G3/4: 0.7%) 

Cardiac failure 

Vascular disorders  Hypotension 
(G3/4: 0.7%) 

 

Gastrointestinal 
disorders  

Nausea (G3/4: 9.6%); 
Vomiting (G3/4: 7.6%); 

Constipation  

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Diarrhoea (G3/4: 6.4%); 
Stomatitis (G3/4: 2%) 

Skin and 
subcutaneous tissue 
disorders 

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

  

Musculoskeletal and 
connective tissue 
disorders 

Myalgia (severe: 0.5%)  
 

 

General disorders 
and administration 
site conditions 

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

Infusion site reaction; 
Pain 

 

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

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

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

 
Common adverse 
reactions  

Blood and lymphatic system 
disorders  

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

 

Metabolism and nutrition 
disorders 

Anorexia  

Psychiatric disorders Insomnia  
Nervous system disorders  
 

Paresthesia; Headache; Dysgeusia; 
Hypoaesthesia 

 

Eye disorders  
 

Lacrimation increased; 
Conjunctivitis 

 

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

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

 

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

 

Skin and subcutaneous tissue 
disorders  

Alopecia; Erythema; Rash; Nail 
disorders 

 

Musculoskeletal and connective 
tissue disorders 

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

 

General disorders and 
administration site conditions 

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

Lethargy 

Investigations Weight increased  
 

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Description of selected adverse reactions in breast cancer for Docetaxel 100 mg/m2 in combination 
with trastuzumab 
 
Cardiac disorders 
Symptomatic cardiac failure was reported in 2.2% of the patients who received docetaxel plus 
trastuzumab compared to 0% of patients given docetaxel alone. In the docetaxel plus trastuzumab arm, 
64% had received a prior anthracycline as adjuvant therapy compared with 55% in the docetaxel arm 
alone. 
 
Blood and lymphatic system disorders 
Very common: Haematological toxicity was increased in patients receiving trastuzumab and 
docetaxel, compared with docetaxel alone (32% grade 3/4 neutropenia versus 22%, using NCI-CTC 
criteria). Note that this is likely to be an underestimate since docetaxel alone at a dose of 100 mg/m2 is 
known to result in neutropenia in 97% of patients, 76% grade 4, based on nadir blood counts. The 
incidence of febrile neutropenia/neutropenic sepsis was also increased in patients treated with 
Herceptin plus docetaxel (23% versus 17% for patients treated with docetaxel alone). 
 
Tabulated list of adverse reactions in breast cancer for Docetaxel 75 mg/m² in combination with 
capecitabine 
MedDRA system organ 
classes  
 

Very common adverse 
reactions  

Common adverse reactions 
 

Infections and infestations  Oral candidiasis (G3/4: < 1%) 

Blood and lymphatic system 
disorders 

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

Thrombocytopenia (G3/4: 3%) 

Metabolism and nutrition 
disorders 

Anorexia (G3/4: 1%);  
Decreased appetite Dehydration (G3/4: 2%) 

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

 

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

Very common adverse 
reactions  

Common adverse reactions 
 

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

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

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

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

Anorexia (G3/4: 0.6%)  

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

Peripheral motor neuropathy 
(G3/4: 0%) 

Eye disorders  Lacrimation increased (G 
3/4; 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 
tissue 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 Docetaxel 75 mg/m² in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer - pooled data 
 
MedDRA system 
organ classes 

Very common 
adverse reactions  
  

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations  

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

  

Blood and lymphatic 
system disorders 

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

  

Immune system 
disorders 

 Hypersensitivity 
(G3/4: 0.6%) 

 

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MedDRA system 
organ classes 

Very common 
adverse reactions  
  

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 1.5%)   

Nervous system 
disorders  

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

Peripheral motor 
neuropathy 
(G3/4: 0%) 
 

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

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

Lacrimation increased 
(G3/4: <0.1%) 
 

 

Cardiac disorders  Arrhythmia 
(G3/4: 0.2%)  
 

 

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

Lymphoedema 
(G3/4: 0%) 

Respiratory, thoracic 
and mediastinal 
disorders 

 Cough (G3/4: 0%)  

Gastrointestinal 
disorders  

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

Abdominal pain 
(G3/4: 0.4%) 

 

Skin and subcutaneous 
tissue disorders 

Alopecia 
(G3/4: <0.1%); 
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%) 
 

 

 

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Description of selected adverse reactions for adjuvant therapy with Docetaxel 75 mg/m2 in 
combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and 
node-negative (GEICAM 9805) breast cancer 
 
Nervous system disorders 
Peripheral sensory neuropathy was observed to be ongoing during follow-up in 10 patients out of the 
84 patients with peripheral sensory neuropathy at the end of the chemotherapy in the node positive 
breast cancer study (TAX316). 
 
Cardiac disorders 
In study TAX316, 26 patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm 
experienced congestive heart failure.  All except one patient in each arm were diagnosed with CHF 
more than 30 days after the treatment period.  Two patients in the TAC arm and 4 patients in the FAC 
arm died because of cardiac failure. 
 
Skin and subcutaneous tissue disorders 
In study TAX316, alopecia persisting into the follow-up period after the end of chemotherapy was 
reported in 687 TAC patients and 645 FAC patients. 
At the end of the follow-up period, alopecia was observed to be ongoing in 29 TAC patients (4.2%) 
and 16 FAC patients (2.4%). 
 
Reproductive system and breast disorders 
Amenorrhoea was observed to be ongoing during follow-up in 121 patients out of the 202 patients 
with amenorrhoea at the end of the chemotherapy in study TAX316. 
 
General disorders and administration site conditions 
In study TAX316, peripheral oedema was observed to be ongoing in 19 patients out of the 119 patients 
with peripheral oedema in the TAC arm and 4 patients out of the 23 patients with peripheral oedema in 
the FAC arm. 
In study GEICAM 9805, lymphoedema was observed to be ongoing in 4 of the 5 patients with 
lymphoedema at the end of the chemotherapy. 
 
Acute leukaemia / Myelodysplastic syndrome. 
After 10 years of follow up in study TAX316, acute leukaemia was reported in 4 of 744 TAC patients 
and in 1 of 736 FAC patients.  Myelodysplastic syndrome was reported in 2 of 744 TAC patients and 
in 1 of 736 FAC patients. 
At a median follow-up time of 77 months, acute leukaemia occurred in 1 of 532 (0.2%) patients who 
received docetaxel, doxorubicin, and cyclophosphamide in the GEICAM 9805 study. No cases were 
reported in patients who received fluorouracil, doxorubicin and cyclophosphamide. No patient was 
diagnosed with myelodysplastic syndrome in either treatment groups. 
 
Neutropenic complications 
Table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic 
infection was decreased in patients who received primary G-CSF prophylaxis after it was made 
mandatory in the TAC arm - GEICAM study. 
 

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

 
 Without primary 

G-CSF prophylaxis 
(n = 111) 

n (%) 
 

With primary 
G-CSF prophylaxis 

(n = 421) 
n (%) 

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

 
Febrile neutropenia 28 (25.2) 23 (5.5) 

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Neutropenic infection 14 (12.6) 21 (5.0) 

 
Neutropenic infection 
(Grade 3-4) 
 

2 (1.8) 5 (1.2) 

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

Very common adverse 
reactions 
 

Common adverse reactions 
 

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

 

Blood and lymphatic system 
disorders 

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

 

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

Anorexia (G3/4: 11.7%)  

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

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

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

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

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

Constipation (G3/4: 1.0 %); 
Gastrointestinal pain 
(G3/4: 1.0%); 
Oesophagitis / dysphagia / 
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 Docetaxel 75 mg/m2 in 
combination with cisplatin and 5-fluorouracil 
 
Blood and lymphatic system disorders 
Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5% of patients respectively, 
regardless of G-CSF use. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of 
the cycles). Febrile neutropenia and neutropenic infection occurred respectively in 12.1% and 3.4% of 
patients when patients received prophylactic G-CSF, in 15.6% and 12.9% of patients without 
prophylactic G-CSF, (see section 4.2). 
 
Tabulated list of adverse reactions in head and neck cancer for Docetaxel 75 mg/m² in combination 
with cisplatin and 5-fluorouracil 
 

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• Induction chemotherapy followed by radiotherapy (TAX 323) 

MedDRA system 
organ classes  

Very common 
adverse reactions 
 

Common adverse 
reactions 
 

Uncommon adverse 
reactions 
 

Infections and 
infestations 

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

  

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

 Cancer pain 
(G3/4: 0.6%) 

 

Blood and lymphatic 
system disorders 

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

Febrile neutropenia  

Immune system 
disorders 

 Hypersensitivity 
(no severe) 

 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 0.6%)   

Nervous system 
disorders 

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

Dizziness  

Eye disorders  Lacrimation increased; 
Conjunctivitis 

 

Ear and labyrinth 
disorders 

 Hearing impaired   

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

Arrhythmia 
(G3/4: 0.6%) 

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

 

Gastrointestinal 
disorders  

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

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

 

Skin and subcutaneous 
tissue disorders  

Alopecia 
(G3/4: 10.9%) 

Rash pruritus; 
Dry skin; 
Skin exfoliative 
(G3/4:0.6%) 

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.6%)  

General disorders and 
administration site 
conditions 

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

  

Investigations  Weight increased  
 
• Induction chemotherapy followed by chemoradiotherapy (TAX 324) 

MedDRA system Very common adverse Common adverse Uncommon adverse 

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organ classes  reactions 
 

reactions 
 

reactions 
 

Infections and 
infestation 

Infection (G3/4: 3.6%) 
 

Neutropenic infection  

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

 Cancer pain 
(G3/4: 1.2%) 

 

Blood and lymphatic 
system disorders 

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

  

Immune system 
disorders 

  Hypersensitivity 

Metabolism and 
nutrition disorders 

Anorexia (G3/4: 12.0%)   

Nervous system 
disorders 

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

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

 

Eye disorders  Lacrimation increased Conjunctivitis 
Ear and labyrinth 
disorders 

Hearing impaired 
(G3/4: 1.2%) 

  

Cardiac disorders  Arrhythmia 
(G3/4: 2.0%) 

Ischemia myocardial 

Vascular disorders   Venous disorder 
Gastrointestinal 
disorders  

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

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

 

Skin and subcutaneous 
tissue disorders  

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

Dry skin; 
Desquamation 

 

Musculoskeletal and 
connective tissue 
disorders 

 Myalgia (G3/4: 0.4%)  

General disorders and 
administration site 
conditions 

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

  

Investigations Weight decreased  Weight increased 
 
Post-marketing experience 
 

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Neoplasms benign, malignant and unspecified (incl cysts and polyps) 
Cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported in association 
with docetaxel when used in combination with other chemotherapy agents and/or radiotherapy. 
 
Blood and lymphatic system disorders 
Bone marrow suppression and other haematologic adverse reactions have been reported. Disseminated 
intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been 
reported. 
 
Immune system disorders 
Some cases of anaphylactic shock, sometimes fatal, have been reported. 
 
Nervous system disorders 
Rare cases of convulsion or transient loss of consciousness have been observed with docetaxel 
administration. These reactions sometimes appear during the infusion of the medicinal product. 
 
Eye Disorders 
Very rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring 
during infusion of the medicinal product and in association with hypersensitivity reactions have been 
reported. These were reversible upon discontinuation of the infusion. Cases of lacrimation with or 
without conjunctivitis, as cases of lachrymal 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. 
 
Vascular disorders 
Venous thromboembolic events have rarely been reported. 
 
Respiratory, thoracic and mediastinal disorders 
Acute respiratory distress syndrome and cases of interstitial pneumonia/pneumonitis, interstitial lung 
disease, pulmonary fibrosis and respiratory failure sometimes fatal have rarely been reported. Rare 
cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy. 
 
Gastrointestinal disorders 
Rare occurrences of dehydration as a consequence of gastrointestinal events, gastrointestinal 
perforation, colitis ischaemic, colitis and neutropenic enterocolitis have been reported. Rare cases of 
ileus and intestinal obstruction have been reported. 
 
Hepatobiliary disorders 
Very rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, 
have been reported. 
 
Skin and subcutaneous tissue disorders 
Very rare cases of cutaneous lupus erythematous and bullous eruptions such as erythema multiform, 
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 lymphedema have been reported with docetaxel.  Cases of 
persisting alopecia have been reported. 
 
Renal and urinary disorders 

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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. 
 
Fluid retention has not been accompanied by acute episodes of oliguria or hypotension. Dehydration 
and pulmonary oedema have rarely been reported. 
 
Metabolism and nutrition disorders 
Cases of hyponatraemia have been reported, mostly associated with dehydration, vomiting and 
pneumonia. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 

There were a few reports of overdose. There is no known antidote for docetaxel overdose. In case of 
overdose, the patient should be kept in a specialised unit and vital functions closely monitored. In 
cases of overdose, exacerbation of adverse events may be expected. The primary anticipated 
complications of overdose would consist of bone marrow suppression, peripheral neurotoxicity and 
mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Taxanes, ATC Code: L01CD 02 
 
Mechanism of action 
 
Docetaxel is an antineoplastic agent which acts by promoting the assembly of tubulin into stable 
microtubules and inhibits their disassembly which leads to a marked decrease of free tubulin. The 
binding of docetaxel to microtubules does not alter the number of protofilaments. 
 
Docetaxel has been shown in vitro to disrupt the microtubular network in cells which is essential for 
vital mitotic and interphase cellular functions. 
 
Pharmacodynamic effects 
 
Docetaxel was found to be cytotoxic in vitro against various murine and human tumour cell lines and 
against freshly excised human tumour cells in clonogenic assays. Docetaxel achieves high intracellular 
concentrations with a long cell residence time. In addition, docetaxel was found to be active on some 
but not all cell lines over expressing the p-glycoprotein which is encoded by the multidrug resistance 
gene. In vivo, docetaxel is schedule independent and has a broad spectrum of experimental antitumour 
activity against advanced murine and human grafted tumours. 
 
Clinical efficacy and safety 
 
Breast Cancer 

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Two randomised phase III comparative studies, involving a total of 326 alkylating or 
392 anthracycline failure metastatic breast cancer patients, have been performed with docetaxel at the 
recommended dose and regimen of 100 mg/m² every 3 weeks. 
 
In alkylating-failure patients, docetaxel was compared to doxorubicin (75 mg/m² every 3 weeks). 
Without affecting overall survival time (docetaxel 15 months vs. doxorubicin 14 months, p=0.38) or 
time to progression (docetaxel 27 weeks vs. doxorubicin 23 weeks, p=0.54), docetaxel increased 
response rate (52% vs. 37%, p=0.01) and shortened time to response (12 weeks vs. 23 weeks, 
p=0.007). Three docetaxel patients (2%) discontinued the treatment due to fluid retention, whereas 15 
doxorubicin patients (9%) discontinued due to cardiac toxicity (three cases of fatal congestive heart 
failure). 
 
In anthracycline-failure patients, docetaxel was compared to the combination of mitomycin C and 
vinblastine (12 mg/m² every 6 weeks and 6 mg/m² every 3 weeks). Docetaxel increased response rate 
(33% vs. 12%, p<0.0001), prolonged time to progression (19 weeks vs. 11 weeks, p=0.0004) and 
prolonged overall survival (11 months vs. 9 months, p=0.01). 
 
During these two phase III studies, the safety profile of docetaxel was consistent with the safety 
profile observed in phase II studies (see section 4.8). 
 
An open-label, multicenter, randomized phase III study was conducted to compare docetaxel 
monotherapy and paclitaxel in the treatment of advanced breast cancer in patients whose previous 
therapy should have included an anthracycline. A total of 449 patients were randomized to receive 
either docetaxel monotherapy 100 mg/m² as a 1 hour infusion or paclitaxel 175 mg/m² as a 3 hour 
infusion. Both regimens were administered every 3 weeks. 
Without affecting the primary endpoint, overall response rate (32% vs 25%, p=0.10), docetaxel 
prolonged median time to progression (24.6 weeks vs 15.6 weeks; p<0.01) and median survival 
(15.3 months vs 12.7 months; p=0.03). 
More grade 3/4 adverse events were observed for docetaxel monotherapy (55.4%) compared to 
paclitaxel (23.0%). 
 
Non-small cell lung cancer 
 

Patients previously treated with chemotherapy with or without radiotherapy 

In a phase III study, in previously treated patients, time to progression (12.3 weeks versus 7 weeks) 
and overall survival were significantly longer for docetaxel at 75 mg/m² compared to Best Supportive 
Care. The 1-year survival rate was also significantly longer in docetaxel (40%) versus BSC (16%). 
There was less use of morphinic analgesic (p<0.01), non-morphinic analgesics (p<0.01), other disease 
related medications (p=0.06) and radiotherapy (p<0.01) in patients treated with docetaxel at 75 mg/m² 
compared to those with BSC. 
The overall response rate was 6.8% in the evaluable patients, and the median duration of response was 
26.1 weeks. 
 
Docetaxel in combination with platinum agents in chemotherapy-naïve patients 
 
In a phase III study, 1218 patients with unresectable stage IIIB or IV NSCLC, with KPS of 70% or 
greater, and who did not receive previous chemotherapy for this condition, were randomised to either 
Docetaxel  (T) 75 mg/m2 as a 1 hour infusion immediately followed by cisplatin (Cis) 75 mg/m2 over 
30-60 minutes every 3 weeks (TCis), Docetaxel 75 mg/m2 as a 1 hour infusion in combination with 
carboplatin (AUC 6 mg/ml. min) over 30-60 minutes every 3 weeks, or vinorelbine (V) 25 mg/m2 
administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on 
day 1 of cycles repeated every 4 weeks (VCis). 
 
Survival data, median time to progression and response rates for two arms of the study are illustrated 
in the following table: 
 

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 TCis 
n=408 

 

VCis 
n=404 

 

Statistical Analysis 

Overall survival 
(Primary end-point): 

   

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

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

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

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

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

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

Docetaxel 
every 3 weeks 

 

Docetaxel 
every week 

 

Mitoxantrone 
every 3 weeks 

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

335 
18.9 

(17.0-21.2) 
0.761 

(0.619-0.936) 
0.0094 

334 
17.4 

(15.7-19.0) 
0.912 

(0.747-1.113) 
0.3624 

337 
16.5 

(14.4-18.6) 
-- 
-- 
-- 

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

291 
45.4 

(39.5-51.3) 
0.0005 

282 
47.9 

(41.9-53.9) 
<0.0001 

300 
31.7 

(26.4-37.3) 
-- 

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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. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 
20-115 mg/m2 in Phase I studies. The kinetic profile of docetaxel is dose independent and consistent 
with a three-compartment pharmacokinetic model with half lives for the α, β and γ phases of 4 min, 
36 min and 11.1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel 
from the peripheral compartment.  
 
Distribution 
 
Following the administration of a 100 mg/m2 dose given as a one hour infusion a mean peak plasma 
level of 3.7 μg/ml was obtained with a corresponding AUC of 4.6 h.μg/ml. Mean values for total body 
clearance and steady-state volume of distribution were 21 l/h/m2 and 113 l, respectively. Inter 
individual variation in total body clearance was approximately 50%. Docetaxel is more than 95% 
bound to plasma proteins. 
 
Elimination 
 
A study of 14C-docetaxel has been conducted in three cancer patients. Docetaxel was eliminated in 
both the urine and faeces following cytochrome P450-mediated oxidative metabolism of the tert-butyl 
ester group, within seven days, the urinary and faecal excretion accounted for about 6% and 75% of 
the administered radioactivity, respectively. About 80% of the radioactivity recovered in faeces is 
excreted during the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites 
and very low amounts of unchanged medicinal product. 
 
Special populations 
 
Age and gender 
A population pharmacokinetic analysis has been performed with docetaxel in 577 patients. 
Pharmacokinetic parameters estimated by the model were very close to those estimated from Phase I 
studies. The pharmacokinetics of docetaxel were not altered by the age or sex of the patient.  
 
Hepatic impairment 
In a small number of patients (n=23) with clinical chemistry data suggestive of mild to moderate liver 
function impairment (ALT, AST ≥1.5 times the ULN associated with alkaline phosphatase ≥2.5 times 
the ULN), total clearance was lowered by 27% on average (see section 4.2).  
 

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Fluid retention 
Docetaxel clearance was not modified in patients with mild to moderate fluid retention and there are 
no data available in patients with severe fluid retention. 
 
Combination therapy 
 
Doxorubicin 
When used in combination, docetaxel does not influence the clearance of doxorubicin and the plasma 
levels of doxorubicinol (a doxorubicin metabolite). The pharmacokinetics of docetaxel, doxorubicin 
and cyclophosphamide were not influenced by their coadministration. 
 
Capecitabine 
Phase I study evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice 
versa showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no 
effect by docetaxel on the pharmacokinetics of a relevant capecitabine metabolite 5’-DFUR. 
 
Cisplatin 
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following 
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is 
similar to that observed with cisplatin alone. 
 
Cisplatin and 5-fluorouracil 
The combined administration of docetaxel, cisplatin and 5-fluorouracil in 12 patients with solid 
tumours had no influence on the pharmacokinetics of each individual medicinal product. 
 
Prednisone and dexamethasone 
The effect of prednisone on the pharmacokinetics of docetaxel administered with standard 
dexamethasone premedication has been studied in 42 patients.  
 
Prednisone 
No effect of prednisone on the pharmacokinetics of docetaxel was observed. 
 
5.3 Preclinical safety data 
 
The carcinogenic potential of docetaxel has not been studied. 
 
Docetaxel has been shown to be mutagenic in the in vitro micronucleus and chromosome aberration 
test in CHO-K1 cells and in the in vivo micronucleus test in the mouse. However, it did not induce 
mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay. These results are consistent 
with the pharmacological activity of docetaxel. 
 
Undesirable effects on the testis observed in rodent toxicity studies suggest that docetaxel may impair 
male fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Concentrate  
Polysorbate 80 
Ethanol, anhydrous 
 
Solvent  
Water for injections. 
 
6.2 Incompatibilities 

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This medicinal product must not be mixed with other medicinal products except those mentioned in 
Section 6.6. 
 
6.3 Shelf-life 
 
• 18 months. 
• Premix solution: Chemical and physical in-use stability has been demonstrated for 8 hours when 

stored either between 2°C and 8°C or at room temperature (below 25°C). From a 
microbiological point of view, the product should be used immediately. If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user and would 
normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled 
and validated aseptic conditions. 

• Infusion solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 
room temperature (below 25°C). From a microbiological point of view, the product should be 
used immediately. If not used immediately, in-use storage times and conditions prior to use are 
the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless 
dilution has taken place in controlled and validated aseptic conditions. 

 
6.4 Special precautions for storage and other handling 
 

Do not store above 25°C . 
Do not freeze. 
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 
 
Each carton contains: 
• One vial of concentrate and, 
• One vial of solvent 
 
• Docetaxel Teva Pharma 80 mg vial  
 15 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 

 
This vial contains 2.88  ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 
(fill volume: 94.4 mg/3.40 ml). This fill volume has been established during the development of 
docetaxel to compensate for liquid loss during preparation of the premix due to foaming, 
adhesion to the walls of the vial and "dead-volume". This overfill ensures that after dilution with 
the entire contents of the accompanying solvent for docetaxel vial, there is a minimal extractable 
premix volume of 8 ml containing 10 mg/ml docetaxel which corresponds to the labelled 
amount of 80 mg per vial. 
 
Solvent for Docetaxel Teva Pharma 80 mg vial 
15 ml clear glass Type I vial with a bromobutyl rubber stopper and a flip-off cap. 
 
Solvent vial contains 5.12 ml of water for injections (fill volume: 6.29 ml). The addition of the 
entire contents of the solvent vial to the contents of the Docetaxel Teva Pharma 80 mg 
concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 

6.6 Special precautions for disposal and other handling 
 
Docetaxel Teva Pharma is an antineoplastic agent and, as with other potentially toxic compounds, 
caution should be exercised when handling it and preparing Docetaxel solutions. The use of gloves is 
recommended. 
 

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If Docetaxel Teva Pharma concentrate, premix solution or infusion solution should come into contact 
with skin, wash immediately and thoroughly with soap and water. If Docetaxel concentrate, premix 
solution or infusion solution should come into contact with mucous membranes, wash immediately 
and thoroughly with water. 
 
Preparation for the intravenous administration 

a) Preparation of the Docetaxel Teva Pharma premix solution (10 mg docetaxel/ml) 

If the vials are stored under refrigeration, allow the required number of Docetaxel Teva Pharma boxes 
to stand at room temperature (below 25°C) for 5 minutes. 
 
Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva Pharma vial by partially inverting the vial. 
 
Inject the entire contents of the syringe into the corresponding Docetaxel Teva Pharma vial. 
 
Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do 
not shake. 
 
Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then check that 
the solution is homogenous and clear (foaming is normal even after 5 minutes due to the presence of 
polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after preparation. 
However the chemical and physical stability of the premix solution has been demonstrated for 8 hours 
when stored either between 2°C and 8°C or at room temperature (below 25°C). 
 
b) Preparation of the infusion solution 

More than one premix vial may be necessary to obtain the required dose for the patient. Based on the 
required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume 
containing 10 mg/ml docetaxel from the appropriate number of premix vials using graduated syringes 
fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix 
solution. 
 
Inject the required premix volume into a non-PVC 250 ml infusion bag containing either 5% glucose 
solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. 
 
If a dose greater than 200 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 Docetaxel Teva Pharma infusion solution should be used within 4 hours and should be aseptically 
administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting 
conditions. 
 
As with all parenteral products, Docetaxel Teva Pharma premix solution and 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 

Teva Pharma B.V. 
Computerweg 10 

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3542 DR Utrecht 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/10/662/002 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
21st January 2011 
 
 
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. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Pharmachemie BV. 
Swensweg 5 
Postbus 552  
2003 RN Haarlem 
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82 
2100 Gödöllő 
Hungary 
 
Teva Operations Poland Sp. z.o.o. 
Sienkiewicza 25 
99-300 Kutno 
Poland 
 
Teva Czech Industries s.r.o 
Ostravská 29 
Č.p. 305 
747 70 Opava-Komárov 
Czech Republic 
 
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 marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided fro 
under Article 107c(7) of Directive 2001/83/EC and published on the European Medicines web-portal. 
 
D. CONITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
Not applicable. 
 
• Obligation to conduct post-authorisation measures 
 
Not applicable. 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 20 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva Pharma 20 mg concentrate and solvent for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each single-dose vial of Docetaxel Teva Pharma concentrate contains 20 mg docetaxel (anhydrous). 
Each ml of concentrate contains 27.73 mg docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Docetaxel concentrate vial: 
polysorbate 80, anhydrous ethanol. 
 
Solvent vial: 
water for injections. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate and solvent for solution for infusion. 
Each carton contains: 
• one vial of 0.72 ml concentrate (20 mg of docetaxel), 
• one vial of 1.28 ml solvent (water for injections). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use.  
CAUTION: Dilution of concentrate required using the entire contents of the solvent vial. 
Reconstituted solution must be further diluted in the infusion diluent before administration. 
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.  To be administered under the supervision of a physician experienced in the use of 
cytotoxic agents 

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8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze 
 
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. 
Discard unused contents appropriately 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/662/001 
 
 
13. BATCH NUMBER 
 
Batch: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – CONCENTRATE 20 mg 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Teva Pharma 20 mg concentrate for solution for infusion 
docetaxel 
 
 
2. METHOD OF ADMINISTRATION 
 
Intravenous use. 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Batch: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.72 ml (Fill: 0.88 ml) 
 
 
6. OTHER 
 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – SOLVENT FOR 20 mg 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Docetaxel Teva Pharma 20 mg 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Batch: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
water for injections 
1.28 ml (Fill: 1.71 ml) 
 
 
6. OTHER 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 80 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Docetaxel Teva Pharma 80 mg concentrate and solvent for solution for infusion 
docetaxel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each single dose vial of Docetaxel Teva Pharma concentrate contains 80 mg docetaxel (anhydrous). 
Each ml of concentrate contains 27.73 mg docetaxel. 
 
 
3. LIST OF EXCIPIENTS 
 
Docetaxel concentrate vial: 
polysorbate 80, anhydrous ethanol. 
 
Solvent vial: 
water for injections. 
 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate and solvent for solution for infusion. 
Each carton contains: 
• one vial (2.88 ml) of concentrate (80 mg of docetaxel), 
• one vial (5.12 ml) of solvent (water for injections). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use.  
CAUTION: Dilution of concentrate required using the entire contents of the solvent vial. 
Reconstituted solution must be further diluted in the infusion diluent before administration. 
  
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 
 

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CYTOTOXIC.  To be administered under the supervision of a physician experienced in the use of 
cytotoxic agents 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Do not freeze 
 
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. 
Discard unused contents appropriately 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/662/002 
 
 
13. BATCH NUMBER 
 
Batch: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – CONCENTRATE 80 mg 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Docetaxel Teva Pharma 80 mg concentrate for solution for infusion 
docetaxel 
 
 
2. METHOD OF ADMINISTRATION 
 
Intravenous use 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Batch: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.88 ml (Fill: 3.40 ml) 
 
 
6. OTHER 
 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – SOLVENT FOR 80 mg 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Docetaxel Teva Pharma 80 mg 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Batch: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
water for injections 
5.12 ml (Fill: 6.29 ml) 
 
6. OTHER 
 
 

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B. PACKAGE LEAFLET 

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Package leaflet: Information for the patient 
 

Docetaxel Teva Pharma 20 mg concentrate and solvent 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 Docetaxel Teva Pharma is and what it is used for 
2. What you need to know before you use Docetaxel Teva Pharma 
3. How to use Docetaxel Teva Pharma 
4. Possible side effects 
5. How to store Docetaxel Teva Pharma 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Teva Pharma is and what it is used for 
 
The name of this medicine is Docetaxel Teva Pharma. Docetaxel is a substance derived from the 
needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Teva Pharma has been prescribed by your doctor for the treatment of advanced breast 
cancer, special forms of lung cancer (non-small cell lung cancer) and prostate cancer: 
- For the treatment of advanced breast cancer, Docetaxel Teva Pharma could be administered 

alone. 
- For the treatment of lung cancer, Docetaxel Teva Pharma could be administered either alone or 

in combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Teva Pharma is administered in combination 

with prednisone or prednisolone. 
 
 
2. What you need to know before you use Docetaxel Teva Pharma 
 
You must NOT be given Docetaxel Teva Pharma if 
• you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel Teva 

Pharma 
• the number of white blood cells is too low 
• you have a severe liver disease. 
 
Warnings and precautions 
 
Before each treatment with Docetaxel Teva Pharma, you will have blood tests to check that you have 
enough blood cells and sufficient liver function to receive Docetaxel Teva Pharma. In case of white 
blood cells disturbances, you may experience associated fever or infections.  
 
Tell your doctor, hospital pharmacist or nurse if you have vision problems.  In case of vision 
problems, in particular blurred vision, you should immediately have your eyes and vision examined. 
 

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If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 
please tell your doctor, hospital pharmacist or nurse immediately.  Your doctor may stop your 
treatment immediately. 
 
You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 
one day prior to Docetaxel Teva Pharma administration and to continue for one or two days after it in 
order to minimise certain undesirable effects which may occur after the infusion of Docetaxel Teva 
Pharma 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. 
 
Other medicines and Docetaxel Teva Pharma 
 
Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 
medicines, including medicines obtained without a prescription. This is because Docetaxel Teva 
Pharma or the other medicine may not work as well as expected and you may be more likely to get a 
side effect. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Teva Pharma must NOT be administered if you are pregnant unless clearly indicated by 
your doctor.  
 
You must not become pregnant during treatment with this medicine and must use an effective method 
of contraception during therapy because Docetaxel Teva Pharma may be harmful for the unborn baby. 
If pregnancy occurs during your treatment, you must immediately inform your doctor. 
 
You must not breast-feed while you are treated with Docetaxel Teva Pharma. 
 
If you are a man being treated with Docetaxel Teva Pharma you are advised not to father a child 
during and up to 6 months after treatment and to seek advice on conservation of sperm prior to 
treatment because docetaxel may alter male fertility. 
  
Driving and using machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
 
3. How to use Docetaxel Teva Pharma 
 
Docetaxel Teva Pharma will be administered to you by a healthcare professional. 
 
Usual dose 
 
The dose will depend on your weight and your general condition. Your doctor will calculate your body 
surface area in square meters (m²) and will determine the dose you should receive. 
 
Method and route of administration 
 
Docetaxel Teva Pharma 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 
 

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You should usually receive your infusion once every 3 weeks. 
 
Your doctor may change the dose and frequency of dosing depending on your blood tests, your 
general condition and your response to Docetaxel Teva Pharma. In particular, please inform your 
doctor in case of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and 
give her/him results of your blood tests. Such information will allow her/him to decide whether a dose 
reduction is needed. If you have any further questions on the use of this medicine, ask your doctor or 
hospital pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Your doctor will discuss these with you and will explain the potential risks and benefits of your 
treatment. 
 
The most commonly reported adverse reactions of Docetaxel Teva Pharma alone are: decrease in the 
number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 
diarrhoea and tiredness. 
 
The severity of adverse events of Docetaxel Teva Pharma may be increased when Docetaxel Teva 
Pharma is given in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions (may affect more than 1  in 10 
people): 
• flushing, skin reactions, itching 
• chest tightness; difficulty in breathing 
• fever or chills 
• back pain 
• low blood pressure. 
More severe reactions may occur. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Teva Pharma the following may occur, and the frequency may vary 
with the combinations of medicines that are received: 
 
Very common (may affect more than 1 in 10 people): 
• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 

fighting infection) and platelets 
• fever: if this happens you must tell your doctor immediately 
• allergic reactions as described above 
• loss of appetite (anorexia) 
• insomnia 
• feeling of numbness or pins and needles or pain in the joints or muscles 
• headache 
• alteration in sense of taste 
• inflammation of the eye or increased tearing of the eyes 
• swelling caused by faulty lymphatic drainage 
• shortness of breath 
• nasal drainage; inflammation of the throat and nose; cough 
• bleeding from the nose 
• sores in the mouth 
• stomach upsets including nausea, vomiting and diarrhoea, constipation 

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• abdominal pain 
• indigestion 
• hair loss (in most cases normal hair growth should return) 
• redness and swelling of the palms of your hands or soles of your feet which may cause your skin 

to peel (this may also occur on the arms, face, or body) 
• change in the colour of your nails, which may detach 
• muscle aches and pains; back pain or bone pain 
• change or absence of menstrual period 
• swelling of the hands, feet, legs 
• tiredness; or flu-like symptoms 
• weight gain or loss. 
 
Common (may affect up to 1 in 10 people): 
• oral candidiasis 
• dehydration 
• dizziness 
• hearing impaired 
• decrease in blood pressure; irregular or rapid heart beat 
• heart failure 
• oesophagatis 
• dry mouth 
• difficulty or painful swallowing 
• haemorrhage 
• raised liver enzymes (hence the need for regular blood tests). 
 
Uncommon (may affect up to 1 in 100 people): 
• fainting 
• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
• inflammation of the colon, small intestine; intestinal perforation 
• blood clots. 
 
Frequency unknown: 
• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing.  

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 
• pneumonia (infection of the lungs) 
• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath) 
• blurred vision due to swelling of the retina within the eye (cystoid macular oedema) 
• decrease of the sodium in your blood. 
 
Reporting of side effects 
If you get any side effects talk to your doctor, hospital pharmacist or nurse.  This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V.  By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Docetaxel Teva Pharma 
 
Keep this medicine out of the sight and reach of children. 
 
This medicine should not be used after the expiry date which is stated on the carton and vials. 
 
Do not store above 25°C. 
Do not freeze. 
 

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Store in the original package in order to protect from light. 
 
The premix solution should be used immediately after preparation. However the chemical and physical 
stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C and 
8°C or at room temperature (below 25°C). 
 
The infusion solution should be used within 4 hours at room temperature (below 25°C). 
 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
no longer used. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Docetaxel Teva Pharma concentrate vial contains: 
- The active substance is docetaxel. Each vial of concentrate contains 20 mg of docetaxel. Each 

ml of concentrate contains 27.73 mg docetaxel. 
 
- The other ingredients are polysorbate 80 and 25.1% (w/w) anhydrous ethanol. 
 
What the solvent vial contains: 
Water for injections. 
 
What Docetaxel Teva Pharma looks like and contents of the pack: 
Docetaxel Teva Pharma concentrate for solution for infusion is a clear viscous, yellow to brown-
yellow solution. 
 
Each carton contains: 

• one 6 ml clear glass vial with a flip-off cap containing 0.72 ml concentrate and, 
• one 6 ml clear glass vial with a flip-off cap containing 1.28 ml of solvent.  
 

 
Marketing Authorisation Holder 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
Manufacturer: 
Pharmachemie B.V. 
Swensweg 5 
PO Box 552 
2003 RN Haarlem  
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82 
H-2100 Gödöllő  
Hungary 
 
Teva Operations Poland Sp. z.o.o. 
Sienkiewicza 25 
99-300 Kutno 
Poland 
 
Teva Czech Industries s.r.o 
Ostravská 29 

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Č.p. 305 
747 70 Opava-Komárov 
Czech Republic 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg  
Teva Pharma Belgium N.V./S.A./AG  
Tél: +32 3 820 73 73 

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

  
Malta  
Drugsales Ltd 
Τel: +356 21 419 070/1/2 

 
Deutschland 
Teva GmbH 
Tel: +49 731 402 08 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 

 
Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

 
Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 

 
Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007-0 

 
España 
Teva Pharma, S.L.U. 
Tél: +34 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 

 
France 
Teva Santé 
Tél: +33 1 55 91 78 00 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 

 
Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 327 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

 
Ísland 
ratiopharm Oy 
Sími: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 

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Italia 
Teva Italia S.r.l. 
Tel: +39 028917981 

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 

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

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The following information is intended for healthcare professionals only: 

PREPARATION GUIDE FOR USE WITH DOCETAXEL TEVA PHARMA 20 mg 
CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION  
__________________________________________________________________________ 

It is important that you read the entire contents of this guide prior to the preparation of either the 
Docetaxel Teva Pharma premix solution or the Docetaxel Teva Pharma infusion solution 
 
 
1. FORMULATION 

Docetaxel Teva Pharma 20 mg concentrate for solution for infusion is a clear viscous, yellow to 
brown-yellow solution containing 27.73 mg/ml docetaxel (anhydrous) in polysorbate 80. The solvent 
for Docetaxel Teva Pharma is water for injections. 
 
 
2. PRESENTATION 

Docetaxel Teva Pharma is supplied as single-dose vials. 
 
Each box contains one Docetaxel Teva Pharma vial (20 mg) and one corresponding solvent for 
Docetaxel Teva Pharma vial in a carton. 
 
Docetaxel Teva Pharma vials should not be stored above 25°C and should be protected from light. 
Docetaxel Teva Pharma should not be used after the expiry date shown on the carton and vials. 
 
2.1 Docetaxel 20 mg vial: 

• The Docetaxel 20 mg vial is a 6 ml clear glass vial with a bromobutyl rubber stopper and a 
flip-off cap. 

 
• The Docetaxel 20 mg vial contains a solution of docetaxel in polysorbate 80 at a concentration 

of 27.73 mg/ml. 
 
• Each vial contains 20 mg/0.72 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill 

volume: 24.4 mg/0.88 ml). This fill volume has been established during the development of 
docetaxel to compensate for liquid loss during preparation of the premix (see section 4) due to 
foaming, adhesion to the walls of the vial and "dead-volume". This overfill ensures that after 
dilution with the entire contents of the accompanying solvent for docetaxel vial, there is a 
minimal extractable premix volume of 2 ml containing 10 mg/ml docetaxel which corresponds 
to the labelled amount of 20 mg per vial. 

 
2.2 Solvent for Docetaxel 20 mg vial: 

• The solvent for Docetaxel 20 mg vial is a 6 ml clear glass vial with a bromobutyl rubber stopper 
and a flip-off cap. 

 
• The solvent for Docetaxel composition is water for injections. 
 
• Each solvent vial contains 1.28 ml of water for injections (fill volume: 1.71 ml). The addition of 

the entire contents of the solvent vial to the contents of the Docetaxel Teva Pharma 20mg vial 
ensures a premix concentration of 10 mg/ml docetaxel. 

 
 

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3. RECOMMENDATIONS FOR THE SAFE HANDLING 
 
Docetaxel Teva Pharma is an antineoplastic agent and, as with other potentially toxic compounds, 
caution should be exercised when handling it and preparing Docetaxel Teva Pharma solutions. The use 
of gloves is recommended. 
 
If Docetaxel Teva Pharma concentrate, premix solution or infusion solution should come into contact 
with skin, wash immediately and thoroughly with soap and water. If Docetaxel Teva Pharma 
concentrate, premix solution or infusion solution should come into contact with mucous membranes, 
wash immediately and thoroughly with water. 
 
 
4. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION 

4.1 Preparation of the Docetaxel Teva Pharma premix solution (10 mg docetaxel/ml) 
 
4.1.1 If the vials are stored under refrigeration, allow the required number of Docetaxel Teva 

Pharma boxes to stand at room temperature (below 25°C) for 5 minutes. 
 

4.1.2 Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva Pharma vial by partially inverting the vial. 
 

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Teva Pharma vial. 
 
4.1.4 Remove the syringe and needle and mix manually by repeated inversions for at least 45 

seconds. Do not shake. 
 
4.1.5 Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then 

check that the solution is homogenous and clear (foaming is normal even after 5 minutes due 
to the presence of polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after 
preparation. However the chemical and physical stability of the premix solution has been 
demonstrated for 8 hours when stored either between +2°C and +8°C or at room temperature 
(below 25°C). 

 
 
 
4.2 Preparation of the infusion solution 
 
4.2.1 More than one premix vial may be necessary to obtain the required dose for the patient. Based 

on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
premix volume containing 10 mg/ml docetaxel from the appropriate number of premix vials 
using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would 
require 14 ml docetaxel premix solution. 

 
4.2.2 Inject the required premix volume into a 250 ml non-PVC infusion bag containing either 5% 

glucose solution or sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 
than 200 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. 

 
4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 
4.2.4  The Docetaxel Teva Pharma infusion solution should be used within 4 hours and should be 

aseptically administered as a 1-hour infusion under room temperature (below 25°C) and 
normal lighting conditions. 

 
4.2.5 As with all parenteral products, Docetaxel Teva Pharma premix solution and infusion solution 

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should be visually inspected prior to use, solutions containing a precipitate should be 
discarded. 

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

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Package leaflet: Information for the patient 
 

Docetaxel Teva Pharma 80 mg concentrate and solvent 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 Docetaxel Teva Pharma is and what it is used for 
2. What you need to know before you use Docetaxel Teva Pharma 
3. How to use Docetaxel Teva Pharma 
4. Possible side effects 
5. How to store Docetaxel Teva Pharma 
6. Contents of the pack and other information 
 
 
1. What Docetaxel Teva Pharma is and what it is used for 
 
The name of this medicine is Docetaxel Teva Pharma. Docetaxel is a substance derived from the 
needles of yew trees. 
Docetaxel belongs to the group of anti-cancer medicines called taxoids. 
 
Docetaxel Teva Pharma has been prescribed by your doctor for the treatment of advanced breast 
cancer, special forms of lung cancer (non-small cell lung cancer) and prostate cancer: 
- For the treatment of advanced breast cancer, Docetaxel Teva Pharma could be administered 

alone. 
- For the treatment of lung cancer, Docetaxel Teva Pharma could be administered either alone or 

in combination with cisplatin. 
- For the treatment of prostate cancer, Docetaxel Teva Pharma is administered in combination 

with prednisone or prednisolone. 
 
 
2. What you need to know before you use Docetaxel Teva Pharma 
 
You must NOT be given Docetaxel Teva Pharma if 
• you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel Teva 

Pharma 
• the number of white blood cells is too low 
• you have a severe liver disease. 
 
Warnings and precautions 
 
Before each treatment with Docetaxel Teva Pharma, you will have blood tests to check that you have 
enough blood cells and sufficient liver function to receive Docetaxel Teva Pharma. In case of white 
blood cells disturbances, you may experience associated fever or infections.  
 
Tell your doctor, hospital pharmacist or nurse if you have vision problems. In case of vision problems, 
in particular blurred vision, you should immediately have your eyes and vision examined. 
 

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If you develop acute or worsening problems with your lungs (fever, shortness of breath or cough), 
please tell your doctor, hospital pharmacist or nurse immediately.  Your doctor may stop your 
treatment  immediately. 
 
You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, 
one day prior to Docetaxel Teva Pharma administration and to continue for one or two days after it in 
order to minimise certain undesirable effects which may occur after the infusion of Docetaxel Teva 
Pharma 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. 
 
Other medicines and Docetaxel Teva Pharma 
 
Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other 
medicines, including medicines obtained without a prescription. This is because Docetaxel Teva 
Pharma or other medicine may not work as well as expected and you may be more likely to get a side 
effect. 
 
Pregnancy, breast-feeding and fertility 
 
Ask your doctor for advice before being given any medicine. 
 
Docetaxel Teva Pharma 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 you must use an effective 
method of contraception during therapy because Docetaxel Teva Pharma may be harmful for the 
unborn baby. If pregnancy occurs during your treatment, you must immediately inform your doctor. 
 
You must not breast-feed while you are treated with Docetaxel Teva Pharma. 
 
If you are a man being treated with Docetaxel Teva Pharma you are advised not to father a child 
during and up to 6 months after treatment and to seek advice on conservation of sperm prior to 
treatment because docetaxel may alter male fertility.  
 
Driving and using machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
 
3. How to use Docetaxel Teva Pharma 
 
Docetaxel Teva Pharma will be administered to you by a healthcare professional. 
 
Usual dose 
 
The dose will depend on your weight and your general condition. Your doctor will calculate your body 
surface area in square meters (m²) and will determine the dose you should receive. 
 
Method and route of administration 
 
Docetaxel Teva Pharma 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 
 

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You should usually receive your infusion once every 3 weeks. 
 
Your doctor may change the dose and frequency of dosing depending on your blood tests, your 
general condition and your response to Docetaxel Teva Pharma. In particular, please inform your 
doctor in case of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and 
give her/him results of your blood tests. Such information will allow her/him to decide whether a dose 
reduction is needed. If you have any further questions on the use of this medicine, ask your doctor or 
hospital pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Your doctor will discuss these with you and will explain the potential risks and benefits of your 
treatment. 
 
The most commonly reported adverse reactions of Docetaxel Teva Pharma alone are: decrease in the 
number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, 
diarrhoea and tiredness. 
 
The severity of adverse events of Docetaxel Teva Pharma may be increased when Docetaxel Teva 
Pharma is given in combination with other chemotherapeutic agents. 
 
During the infusion at the hospital the following allergic reactions (may affect more than 1  in 10 
people): 
• flushing, skin reactions, itching 
• chest tightness; difficulty in breathing 
• fever or chills 
• back pain 
• low blood pressure. 
More severe reactions may occur. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of these effects. 
 
Between infusions of Docetaxel Teva Pharma the following may occur, and the frequency may vary 
with the combinations of medicines that are received: 
 
Very common (may affect more than 1 in 10 people): 
• infections, decrease in the number of red (anaemia), or white blood cells (which are important in 

fighting infection) and platelets 
• fever: if this happens you must tell your doctor immediately 
• allergic reactions as described above 
• loss of appetite (anorexia) 
• insomnia 
• feeling of numbness or pins and needles or pain in the joints or muscles 
• headache 
• alteration in sense of taste 
• inflammation of the eye or increased tearing of the eyes 
• swelling caused by faulty lymphatic drainage 
• shortness of breath 
• nasal drainage; inflammation of the throat and nose; cough 
• bleeding from the nose 
• sores in the mouth 
• stomach upsets including nausea, vomiting and diarrhoea, constipation 

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• abdominal pain 
• indigestion 
• hair loss (in most cases normal hair growth should return) 
• redness and swelling of the palms of your hands or soles of your feet which may cause your skin 

to peel (this may also occur on the arms, face, or body) 
• change in the colour of your nails, which may detach 
• muscle aches and pains; back pain or bone pain 
• change or absence of menstrual period 
• swelling of the hands, feet, legs 
• tiredness; or flu-like symptoms 
• weight gain or loss. 
 
Common (may affect up to 1 in 10 people): 
• oral candidiasis 
• dehydration 
• dizziness 
• hearing impaired 
• decrease in blood pressure; irregular or rapid heart beat 
• heart failure 
• oesophagatis 
• dry mouth 
• difficulty or painful swallowing 
• haemorrhage 
• raised liver enzymes (hence the need for regular blood tests). 
 
Uncommon (may affect up to 1 in 100 people): 
• fainting 
• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling 
• inflammation of the colon, small intestine; intestinal perforation 
• blood clots. 
 
Frequency unknown: 
• interstitial lung disease (inflammation of the lungs causing coughing and difficulty breathing.  

Inflammation of the lungs can also develop when docetaxel therapy is used with radiotherapy) 
• pneumonia (infection of the lungs) 
• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath) 
• blurred vision due to swelling of the retina within the eye (cystoid macular odema) 
• decrease of the sodium in your blood. 
 
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 
system listed in Appendix V.  By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Docetaxel Teva Pharma 
 
Keep this medicine out of the sight and reach of children. 
 
This medicine should not be used after the expiry date which is stated on the carton and vials. 
 
Do not store above 25°C. 
Do not freeze. 
 

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Store in the original package in order to protect from light. 
 
The premix solution should be used immediately after preparation. However the chemical and physical 
stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C 
and 8°C or at room temperature (below 25°C). 
 
The infusion solution should be used within 4 hours at room temperature (below 25°C). 
 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
no longer used. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Docetaxel Teva Pharma concentrate vial contains: 
- The active substance is docetaxel. Each vial of concentrate contains 80 mg of docetaxel.  Each 

ml of concentrate contains 27.73 mg docetaxel. 
 
- The other ingredients are polysorbate 80 and 25.1% (w/w) anhydrous ethanol. 
 
What the solvent vial contains: 
Water for injections. 
 
What Docetaxel Teva Pharma looks like and contents of the pack: 
Docetaxel Teva Pharma concentrate for solution for infusion is a clear viscous, yellow to brown-
yellow solution. 
 
Each carton contains: 

• one 15 ml clear glass vial with a flip-off cap containing 2.88 ml concentrate and, 
• one 15 ml clear glass vial with a flip-off cap containing 5.12 ml of solvent.  

 
 
Marketing Authorisation Holder 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
Manufacturer: 
Pharmachemie B.V. 
Swensweg 5 
PO Box 552 
2003 RN Haarlem 
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82 
2100 Gödöllő  
Hungary 
 
Teva Operations Poland Sp. z.o.o. 
Sienkiewicza 25 
99-300 Kutno 
Poland 
 
Teva Czech Industries s.r.o 
Ostravská 29 

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Č.p. 305 
747 70 Opava-Komárov 
Czech Republic 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg  
Teva Pharma Belgium N.V./S.A./AG  
Tél: +32 3 820 73 73  

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár Zrt.  
Tel.: +36 1 288 64 00 

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

  
Malta  
Drugsales Ltd 
Τel: +356 21 419 070/1/2 

 
Deutschland 
Teva GmbH 
Tel: +49 731 402 08 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 

 
Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

 
Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 

 
Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007 0 

 
España 
Teva Pharma, S.L.U. 
Tél: +34 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 

 
France 
Teva Santé 
Tél: +33 1 55 91 78 00 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 

 
Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +40 21 230 65 24 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

 
Ísland 
ratiopharm Oy 
Sími: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 

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Italia 
Teva Italia S.r.l. 
Tel: +39 028917981 

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 

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

The following information is intended for healthcare professionals only: 

PREPARATION GUIDE FOR USE WITH DOCETAXEL TEVA PHARMA 80 mg 
CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION  
__________________________________________________________________________ 

It is important that you read the entire contents of this guide prior to the preparation of either the 
Docetaxel Teva Pharma premix solution or the Docetaxel Teva Pharma infusion solution 
 
 
1. FORMULATION 

Docetaxel Teva Pharma 80 mg concentrate for solution for infusion is a clear viscous, yellow to 
brown-yellow solution containing 27.73 mg/ml docetaxel (anhydrous) in polysorbate 80. The solvent 
for Docetaxel Teva Pharma is water for injections. 
 
 
2. PRESENTATION 

Docetaxel Teva Pharma is supplied as single-dose vials. 
 
Each box contains one Docetaxel Teva Pharma vial (80 mg) and one corresponding solvent for 
Docetaxel Teva Pharma vial in a carton. 
 
Docetaxel Teva Pharma vials should not be stored above 25°C and should be protected from light. 
Docetaxel Teva Pharma should not be used after the expiry date shown on the carton and vials. 
 
 
2.1 Docetaxel 80 mg vial: 

• The Docetaxel 80 mg vial is a 15 ml clear glass vial with a bromobutyl rubber stopper and a 
flip-off cap. 

 
• The Docetaxel 80 mg vial contains a solution of docetaxel in polysorbate 80 at a concentration 

of 27.73 mg/ml. 
 

Each vial contains 80 mg/2.88 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill 
volume: 94.4 mg/3.40 ml). This fill volume has been established during the development of 

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docetaxel to compensate for liquid loss during preparation of the premix due to foaming, 
adhesion to the walls of the vial and "dead-volume". This overfill ensures that after dilution with 
the entire contents of the accompanying solvent for docetaxel vial, there is a minimal extractable 
premix volume of 8 ml containing 10 mg/ml docetaxel which corresponds to the labelled 
amount of 80 mg per vial. 

 
2.2 Solvent for Docetaxel 80 mg vial: 

• The solvent for Docetaxel 80 mg vial is a 15 ml clear glass vial with a bromobutyl rubber 
stopper and a flip-off cap. 

 
• The solvent for Docetaxel composition is water for injections. 
 

Each solvent vial contains 5.12 ml of water for injections (fill volume: 6.29 ml). The addition of 
the entire contents of the solvent vial to the contents of the docetaxel 80 mg concentrate for 
solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel. 

 
 

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3. RECOMMENDATIONS FOR THE SAFE HANDLING 
 
Docetaxel Teva Pharma is an antineoplastic agent and, as with other potentially toxic compounds, 
caution should be exercised when handling it and preparing Docetaxel Teva Pharma solutions. The use 
of gloves is recommended. 
 
If Docetaxel Teva Pharma concentrate, premix solution or infusion solution should come into contact 
with skin, wash immediately and thoroughly with soap and water. If Docetaxel Teva Pharma 
concentrate, premix solution or infusion solution should come into contact with mucous membranes, 
wash immediately and thoroughly with water. 
 
 
4. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION 

4.1 Preparation of the Docetaxel Teva Pharma premix solution (10 mg docetaxel/ml) 
 
4.1.1 If the vials are stored under refrigeration, allow the required number of Docetaxel Teva 

Pharma boxes to stand at room temperature (below 25°C) for 5 minutes. 
 

4.1.2 Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for 
Docetaxel Teva Pharma vial by partially inverting the vial. 
 

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Teva Pharma vial. 
 
4.1.4 Remove the syringe and needle and mix manually by repeated inversions for at least 45 

seconds. Do not shake. 
 
4.1.5 Allow the premix vial to stand for 5 minutes at room temperature (below 25°C) and then 

check that the solution is homogenous and clear (foaming is normal even after 5 minutes due 
to the presence of polysorbate 80 in the formulation). 
 
The premix solution contains 10 mg/ml docetaxel and should be used immediately after 
preparation. However the chemical and physical stability of the premix solution has been 
demonstrated for 8 hours when stored either between +2°C and +8°C or at room temperature 
(below 25°C). 

 
 
 
4.2 Preparation of the infusion solution 
 
4.2.1 More than one premix vial may be necessary to obtain the required dose for the patient. Based 

on the required dose for the patient expressed in mg, aseptically withdraw the corresponding 
premix volume containing 10 mg/ml docetaxel from the appropriate number of premix vials 
using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would 
require 14 ml docetaxel premix solution. 

 
4.2.2 Inject the required premix volume into a 250 ml non-PVC infusion bag containing either 5% 

glucose solution or  sodium chloride 9 mg/ml (0.9%) solution for infusion. If a dose greater 
than 200 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. 

 
4.2.3 Mix the infusion bag or bottle manually using a rocking motion. 
 
4.2.4  The Docetaxel Teva Pharma infusion solution should be used within 4 hours and should be 

aseptically administered as a 1-hour infusion under room temperature (below 25°C) and 
normal lighting conditions. 

 
4.2.5 As with all parenteral products, Docetaxel Teva Pharma premix solution and infusion solution 

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should be visually inspected prior to use, solutions containing a precipitate should be 
discarded. 

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

 
 

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	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVEUSE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET