Hospira Docetaxel Concentrate for Solution for Infusion 20 mg / 2 ml

PFIZER PRIVATE LIMITED

PFIZER PRIVATE LIMITED

Therapeutic

Prescription Only

INFUSION, SOLUTION

**4.2 Posology and method of administration** Hospira Docetaxel Concentrate for Solution for Infusion is for intravenous use only. The use of docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should 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 dosage 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 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 – _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. _Breast cancer_ For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dosage 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 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 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 dosage is 75 mg/m2 as a single agent. _Prostate cancer_ _Hormone refractory metastatic 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_). _Gastric adenocarcinoma_ The recommended dose of docetaxel is 75 mg/m2 as a 1-hour infusion, followed by cisplatin 75 mg/m2, as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m2 per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of haematological toxicities (see also ‘Dosage 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-fluorouracil as a continuous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy. - Induction chemotherapy followed by chemoradiotherapy (TAX 324) For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m2 as a 1-hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour infusion, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy. For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics. _Ovarian cancer_ The recommended dosage of docetaxel is 100 mg/m2 administered as a one-hour infusion every three weeks. Dosage 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 <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 75 mg/m2 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-hematologic toxicities, the docetaxel dosage in subsequent cycles should be reduced to 65 mg/m2. For cisplatin dosage adjustments, see manufacturer’s 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, 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 gastrointestinal toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):  For cisplatin and 5-fluorouracil dosage adjustments, see manufacturers’ summary of product characteristics. In the pivotal trial in patients who received an induction treatment with docetaxel for inoperable locally advanced squamous SCCHN and who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (e.g., day 6–15) in all subsequent cycles. Special populations _Patients with hepatic impairment_ Based on pharmacokinetic data with docetaxel at 100 mg/m2 as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m2 (see Sections 4.4 and 5.2 – _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 times ULN associated with alkaline phosphatase >2.5 times ULN, and bilirubin >1 times 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. _Children and adolescents_ The experience in children and adolescents is limited. _Elderly_ Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly. In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).