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Docetaxel Actavis 20mg/ml Concentrate for Solution for Infusion Please refer to the Summary of Product Characteristics (SPC) before prescribing.

Prescribing Information.

Presentation: Single dose vial containing docetaxel 20mg/ml. Indications: Breast cancer: Monotherapy for treatment of locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or alkylating agent. In combination with doxorubicin and cyclophosphamide for adjuvant treatment of operable node-positive breast cancer. In combination with doxorubicin for treatment of locally advanced or metastatic breast cancer where no previous cytotoxic therapy received for this. In combination with trastuzumab for treatment of metastatic breast cancer where tumors overexpress HER2 and where no previous chemotherapy for metastatic disease received. In combination with capecitabine for treatment of locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy-previous therapy to have included an anthracycline. Non-small cell lung (NSCL) cancer: Treatment of locally advanced or metastatic NSCL cancer after failure of prior chemotherapy. In combination with cisplatin for treatment of unresectable, locally advanced or metastatic NSCL cancer in patients who have not previously received chemotherapy for this. Prostate cancer: In combination with prednisone or prednisolone for treatment of hormone refractory metastatic prostate cancer. Gastric adenocarcinoma: In combination with cisplatin and 5-fluorouracil for treatment of metastatic gastric adenocarcinoma, including adenocarcinoma of gastroesophageal junction, where no prior chemotherapy for metastatic disease received. Head and neck cancer: In combination with cisplatin and 5-fluorouracil for induction treatment of locally advanced squamous cell carcinoma of head and neck.

Dosage and Administration: Confine use to specialised chemotherapy units and supervised by physicians qualified in anticancer chemotherapy. Premedication: For breast, non-small cell lung, gastric, and head and neck cancers - premedication consisting of an oral corticosteroid, such as dexamethasone 16mg/day for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can be used. Prophylactic G-CSF may be used to mitigate risk of haematological toxicities. For prostate cancer, recommended premedication is oral dexamethasone 8mg, 12 hours, 3 hours and 1 hour before docetaxel infusion. Administer docetaxel as 1-hour infusion every 3 weeks. Breast cancer: Adjuvant treatment of operable node-positive breast cancer - 75mg/m2 given 1-hour after doxorubicin 50mg/m2 and cyclophosphamide 500mg/m2 every 3 weeks for 6 cycles. Treatment of locally advanced or metastatic breast cancer - 100mg/m2 as monotherapy. In first-line treatment - 75mg/m2 in combination with doxorubicin (50mg/m2). In combination with trastuzumab - 100mg/m2 every 3 weeks, with trastuzumab weekly. In combination with capecitabine - 75mg/m2 every 3 weeks, with capecitabine at 1250mg/m2 twice daily (within 30 minutes after a meal) for 2 weeks followed by 1-week rest. Non-small cell lung cancer: chemotherapy naïve, NSCL cancer patients - 75mg/m2 immediately followed by cisplatin 75mg/m2 over 30-60 minutes. Treatment after failure of prior platinum-based chemotherapy -75mg/m² as single agent. Prostate cancer: 75mg/m2 with continuous prednisone or prednisolone 5mg orally twice daily. Gastric adenocarcinoma: 75mg/m2 as 1 hour infusion, followed by cisplatin 75mg/m2, as 1-3 hour infusion (both on day 1 only), followed by 5-fluorouracil 750mg/m2 per day as 24-hour continuous infusion for 5 days, starting at end of cisplatin infusion. Repeat treatment every 3 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. 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 risk of haematological toxicities. Induction chemotherapy followed by radiotherapy (TAX 323) for induction treatment of inoperable locally advanced squamous cell carcinoma of head and neck (SCCHN) - 75mg/m2 as 1 hour infusion followed by cisplatin 75mg/m2 over 1 hour, on day 1, followed by 5-fluorouracil as continuous infusion at 750mg/m2 per day for 5 days. Administer every 3 weeks for 4 cycles. Following chemotherapy, use radiotherapy. Induction chemotherapy followed by chemoradiotherapy (TAX 324) for induction treatment of locally advanced SCCHN - 75mg/m2 as 1 hour intravenous(IV) infusion on day 1, followed by cisplatin 100mg/m2 administered as 30-minute to 3 hour infusion, followed by 5-fluorouracil 1000mg/m2/day as continuous infusion from day 1-4. Administer every 3 weeks for 3 cycles. Following chemotherapy, use chemoradiotherapy. For dose adjustments during treatment see SPC. For cisplatin and 5-fluorouracil dose modifications, see corresponding SPCs. Special populations: Hepatic impairment

elevations of transaminase greater than 1.5 times upper limit of normal (ULN) and alkaline phosphatase greater than 2.5 times ULN – dose is 75mg/m2. For those with serum bilirubin > ULN and/or ALT and AST >3.5 times ULN associated with alkaline phosphatase >6 times ULN - no dose reduction can be recommended and docetaxel should not be used unless strictly indicated. See SPC for combination data. Children and adolescents – limited experience. Elderly - no special instructions. In combination with capecitabine, for patients 60 years of age or more, starting dose reduction of capecitabine to 75% is recommended. Contraindications: Hypersensitivity to active substance or excipients. Not to be used in patients with baseline neutrophil count of <1500cells/mm3 or in severe liver impairment. Contraindications for other medicinal products combined with docetaxel apply.

- for patients with both

Warnings and Precautions: For breast, NSCL and prostate cancers, premedication with a corticosteroid, unless contraindicated, is advised. Haematology: conduct frequent monitoring of complete blood counts. Re-treat with docetaxel when neutrophils recover to 1500cells/mm3. In severe neutropenia with docetaxel, reduce dose for subsequent courses or use symptomatic measures. In docetaxel with cisplatin and 5-fluorouracil, use prophylactic G-CSF to mitigate risk of complicated neutropenia and monitor closely. Hypersensitivity reactions: observe closely especially during first and second infusions - see SPC for further information. Do not re-challenge in severe hypersensitivity. Cutaneous reactions - localised skin erythema of extremities with oedema followed by desquamation has been reported including severe symptoms leading to interruption or discontinuation. Fluid retention - monitor closely in severe fluid retention. Liver impairment: in patients treated with docetaxel at 100mg/m2 as single agent who have serum transaminase levels greater than 1.5 times ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times ULN, there is 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. See Dosage and Administration section above and SPC for recommended doses. Renal impairment: no data in severe renal impairment. Nervous system: dose reduction required in severe peripheral neurotoxicity. Consider CNS and other effects associated with ethanol in product. Cardiac toxicity: heart failure has been observed in combination with trastuzumab, particularly following anthracyclines. May be moderate to severe and associated with death. Perform baseline cardiac assessment in candidate patients and monitor cardiac function during treatment. Others: contraceptive measures must be taken by men and women during treatment and for at least 6 months after cessation. Additional cautions for use in adjuvant treatment of breast cancer: Complicated neutropenia – consider G-CSF and dose reduction. Gastrointestinal (GI)

reactions - symptoms such as early abdominal pain and tenderness, fever,

diarrhoea, with or without neutropenia, may be early manifestations of serious GI toxicity; evaluate and treat promptly. Congestive heart failure - monitor for symptoms during therapy and follow up. Leukaemia - in docetaxel, doxorubicin and cyclophosphamide treated patients, risk of delayed myelodysplasia or myeloid leukaemia requires haematological follow-up. Patients with 4+ nodes - benefit/risk ratio for TAC is not fully defined. Elderly - no data available in patients >70 years in combination with doxorubicin and cyclophosphamide. Ethanol - contains 100mg ethanol absolute per ml concentrate. Solvent contains 9.53% (w/w) ethanol absolute. Take into consideration for alcoholics, children and high-risk groups such as liver disease or epilepsy.

Drug Interactions: Docetaxel may be modified by concomitant administration of compounds which induce, inhibit or are metabolised by cytochrome P450- 3A. Administer with caution in patients concomitantly receiving potent CYP3A4 inhibitors. Carboplatin. Ketoconazole. The ethanol content may alter effects of other medicines.

Pregnancy & Lactation: Pregnancy - No information in pregnant women. Has been shown in animals to be embryotoxic, foetotoxic and to reduce fertility. May cause foetal harm when administered to pregnant women. Must not be used unless clearly indicated. Childbearing potential/contraception - Women of childbearing age should avoid becoming pregnant, and inform treating physician immediately should this occur. An effective method of contraception should be used during treatment. Docetaxel has genotoxic effects and may alter male fertility-men should not father a child during and up to 6 months after treatment. Lactation-breast feeding must be discontinued for duration of docetaxel therapy.

Undesirable Effects: Very common adverse reactions (1/10): 100mg/m² as a single agent - neutropenia, anaemia, febrile neutropenia, peripheral sensory neuropathy, peripheral motor neuropathy, dysgeusia, dyspnoea, stomatitis, diarrhoea, nausea, vomiting, alopecia, skin reaction, nail disorders, myalgia, anorexia, infections including sepsis and pneumonia, fluid retention, asthenia, pain, hypersensitivity. 75mg/m² as a single agent - neutropenia, anaemia, thrombocytopenia, peripheral sensory neuropathy, nausea, stomatitis, vomiting, diarrhoea, alopecia, skin reaction, anorexia, infections, asthenia, fluid retention, pain. See SPC for common, uncommon and rarely reported. For undesirable effects in combination with doxorubicin, cisplatin, trastuzumab, capecitabine, prednisone or prednisolone, cyclophosphamide, cisplatin and 5-fluorouracil see SPC.

Marketing Authorisation Holder: Actavis Group PTC ehf, Reykjavikurvegur 76-78, Hafnarfjordur, IS-220, Iceland.

Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to Actavis on 01271 311257.

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