DOCETAXEL SANDOZ CONCENTRATE FOR SOLUTION FOR INFUSION 10MG/ML [SIN14564P]

Product Info

DOCETAXEL SANDOZ CONCENTRATE FOR SOLUTION FOR INFUSION 10MG/ML

[SIN14564P]

4.1 Therapeutic indications
Breast cancer
Docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast carcinoma.
Docetaxel in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with

• operable node-positive breast cancer

• operable node-negative breast cancer

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Non-small cell lung cancer
Docetaxel is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer.

Ovarian cancer
Docetaxel is indicated for the treatment of patients with metastatic carcinoma of the ovary after failure of first line or subsequent chemotherapy.

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

Gastric adenocarcinoma
Docetaxel in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.

Head and neck cancer
Docetaxel in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

4.2 Posology and method of administration
The use of docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Recommended dose
For breast, non-small cell lung, ovarian, 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Prophylactic G-CSF may be used to mitigate the risk of hematological 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Docetaxel is administered as a one-hour infusion every three weeks (see section 6.6 for further details on preparation of infusion solution – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Care should be taken of administration of the infusion to avoid extravasation.

Breast cancer
In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended dose of docetaxel is 75 mg/m² administered 1-hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 cycles (TAC regimen). Prophylactic use of G-CSF should be considered in view of the high risk of severe neutropenia and infection (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 60 mg/m² is given in combination therapy with doxorubicin (50 mg/m²).

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

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

Prostate cancer
The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily is administered continuously (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Ovarian cancer
The recommended dose of docetaxel is 100mg/m² administered as a one-hour infusion every three weeks.

Gastric adenocarcinoma
The recommended dose of docetaxel is 75 mg/m² as a 1-hour infusion, followed by cisplatin 75 mg/m², as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m² per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion.
Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of hematological toxicities (see also Dose adjustments during treatment).

Head and neck cancer
Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received prophylactic antibiotics.

• Induction chemotherapy followed by radiotherapy (TAX 323)
  For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1-hour infusion followed by cisplatin 75 mg/m² over 1 hour, on day one, followed by 5-fluorouracilas a continuous infusion at 750 mg/m² per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)
  For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1-hour intravenous infusion on day 1, followed by cisplatin 100 mg/m² administered as a 30-minute to 3-hour infusion, followed by 5-fluorouracil 1000 mg/m²/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.

Dose adjustments during treatment
General
Docetaxel should be administered when the neutrophil count is ≥ 1,500 cells/mm³.

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm³ for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel should be reduced from 100 mg/m² to 75 mg/m² and/or from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.

Adjuvant therapy for breast cancer
Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60mg/m² in all subsequent cycles (see sections 4.4 and 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60mg/m².

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

In combination with capecitabine

• For capecitabine dose modifications, see capecitabine summary of product characteristics.

• For patients developing the first appearance of a Grade 2 toxicity, which persists at the time of the next docetaxel /capecitabine treatment, delay treatment until resolved to Grade 0–1, and resume at 100% of the original dose.

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

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

In combination with cisplatin and 5-fluorouracil
If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m². If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m². In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m². Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/mm³ and platelets recover to a level > 100,000 cells/mm³ . Discontinue treatment if these toxicities persist (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.

In the pivotal SCCHN trials patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6–15) in all subsequent cycles.

Special populations:
Patients with hepatic impairment
Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m² (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 trial excluded patients with ALT and/or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by docetaxel in combination in the other indications.

This medicinal product contains 27% ethanol (alcohol). This has to be taken into account in high-risk groups such as patients with liver disease.

Patients with renal impairment
There are no data available in patients with severely impaired renal function treated with docetaxel.

Paediatric population
The safety and efficacy of docetaxel in nasopharyngeal carcinoma in children aged less than 18 years have not yet been established. There is no relevant use of docetaxel in the paediatric population in the indications breast cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less differentiated nasopharyngeal carcinoma.

Older people
Based on a population pharmacokinetic analysis, there are no special instructions for use in older people. In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).

Method of administration
For instructions on preparation and administration of the product, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
Patients with baseline neutrophil count of < 1,500 cells/mm³.
Patients with severe liver impairment (see sections 4.2 and 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Contraindications for other medicinal products also apply, when combined with docetaxel.