Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Teva B.V., Swensweg 5, 2031 GA, Haarlem, The Netherlands
Docetaxel Teva in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with:
For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer (see section 5.1).
Docetaxel Teva in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition.
Docetaxel Teva monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent.
Docetaxel Teva in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours over express HER2 and who previously have not received chemotherapy for metastatic disease.
Docetaxel Teva in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.
Docetaxel Teva is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.
Docetaxel Teva 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.
Docetaxel Teva in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.
Docetaxel Teva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.
Docetaxel Teva in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.
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).
For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can be used (see section 4.4). For prostate cancer, given the concurrent use of prednisone or prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.4).
Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities.
Docetaxel is administered as a one-hour infusion every three weeks.
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended dose of docetaxel is 75 mg/m² administered 1-hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment).
For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel is 100 mg/m² in monotherapy. In first-line treatment, docetaxel 75 mg/m² is given in combination therapy with doxorubicin (50 mg/m²).
In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m² every three weeks, with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product characteristics.
In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m² every three weeks, combined with capecitabine at 1,250 mg/m² twice daily (within 30 minutes after a meal) for 2 weeks followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, see capecitabine summary of product characteristics.
In chemotherapy naive 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.
The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily is administered continuously (see section 5.1).
The recommended dose of docetaxel is 75 mg/m² as a 1-hour infusion, followed by cisplatin 75 mg/m², as a 1-to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m² per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of haematological toxicities (see also Dose adjustments during treatment).
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received prophylactic antibiotics.
For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour infusion followed by cisplatin 75 mg/m² over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m² per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.
For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m² administered as a 30-minute to 3 hour infusion, followed by 5-fluorouracil 1000 mg/m²/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.
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.
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m².
For patients who are dosed initially at docetaxel 75 mg/m² in combination with cisplatin and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm³, or in patients who experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel dose in subsequent cycles should be reduced to 65 mg/m². For cisplatin dose adjustments, see the corresponding summary of product characteristics.
For trastuzumab dose modifications, see trastuzumab summary of product characteristics.
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m². If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m². In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m². Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/mm³ and platelets recover to a level > 100,000 cells/mm³. Discontinue treatment if these toxicities persist (see section 4.4).
Recommended dose modifications for toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):
| Toxicity | Dose adjustment |
|---|---|
| Diarrhoea grade 3 | First episode: reduce 5-FU dose by 20%. Second episode: then reduce docetaxel dose by 20%. |
| Diarrhoea grade 4 | First episode: reduce docetaxel and 5-FU doses by 20%. Second episode: discontinue treatment. |
| Stomatitis/mucositis grade 3 | First episode: reduce 5-FU dose by 20%. Second episode: stop 5-FU only, at all subsequent cycles. Third episode: reduce docetaxel dose by 20%. |
| Stomatitis/mucositis grade 4 | First episode: stop 5-FU only, at all subsequent cycles. Second episode: reduce docetaxel dose by 20%. |
For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.
In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6-15) in all subsequent cycles.
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m² (see sections 4.4 and 5.2). For those patients with serum bilirubin >ULN and/or ALT and AST >3.5 times the ULN associated with alkaline phosphatase >6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated. In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST >1.5 x ULN associated with alkaline phosphatase >2.5 x ULN, and bilirubin> 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by docetaxel in combination in the other indications.
The safety and efficacy of Docetaxel Teva 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 in the paediatric population in the indications breast cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less differentiated nasopharyngeal carcinoma.
Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).
For instructions on preparation and administration of the product, see section 6.6.
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.
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.
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.
Each carton contains:
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/0.72 ml per 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 20 mg/0.72 ml concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel.
Docetaxel Teva 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 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.
If the vials are stored under refrigeration, allow the required number of Docetaxel Teva 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 vial by partially inverting the vial.
Inject the entire contents of the syringe into the corresponding Docetaxel Teva 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).
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 or bottle 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 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 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.
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