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Important safety information

Second primary malignancies: In patients treated with DOCETAXEL INJECTION-containing regimens, monitor for delayed AML, MDS, NHL, and renal cancer. (5.7) Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe cutaneous adverse reactions have been reported. Severe skin toxicity may require dose adjustment or permanent treatment discontinuation. (5.8) Neurologic reactions: Reactions including paresthesia, dysesthesia, and pain may occur. Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. (5.9) Eye disorders: Cystoid macular edema (CME) has been reported and requires treatment discontinuation. (5.10) Asthenia: Severe asthenia may occur and may require treatment discontinuation. (5.11) Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. (5.12, 8.1, 8.3) Alcohol content: The alcohol content in a dose of DOCETAXEL INJECTION may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. (5.13) Tumor lysis syndrome: Tumor lysis syndrome has been reported. Patients at risk should be well hydrated and closely monitored during treatment. (5.14) 5.1 Toxic Deaths Breast Cancer Docetaxel administered at 100 mg/m 2 was associated with deaths considered possibly or probably related to treatment in 2% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m 2 , mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths. Non-small Cell Lung Cancer Docetaxel administered at a dose of 100 mg/m 2 in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m 2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m 2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [see Dosage and Administration (2.2), Clinical Studies (14)]. 5.2 Hepatic Impairment Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Avoid DOCETAXEL INJECTION in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [see Warnings and Precautions (5.1)]. For patients with isolated elevations of transaminase >1.5 × ULN, consider DOCETAXEL INJECTION dose modifications [see Dosage and Administration (2.7)] . Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of DOCETAXEL INJECTION therapy. 5.3 Hematologic Effects Perform frequent peripheral blood cell counts on all patients receiving DOCETAXEL INJECTION. Do not retreat patients with subsequent cycles of DOCETAXEL INJECTION until neutrophils recover to a level > 1,500 cells/mm 3 [s ee Contraindications (4)] . Avoid retreating patients until platelets recover to a level > 100,000 cells/mm 3 . A 25% reduction in the dose of DOCETAXEL INJECTION is recommended during subsequent cycles following severe neutropenia (<500 cells/mm 3 ) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a DOCETAXEL INJECTION cycle [see Dosage and Administration (2.7)]. Neutropenia (<2000 neutrophils/mm 3 ) occurs in virtually all patients given 60 mg/m 2 to 100 mg/m 2 of docetaxel and grade 4 neutropenia (<500 cells/mm 3 ) occurs in 85% of patients given 100 mg/m 2 and 75% of patients given 60 mg/m 2 . Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. DOCETAXEL INJECTION should not be administered to patients with neutrophils <1,500 cells/mm 3 . Febrile neutropenia occurred in about 12% of patients given 100 mg/m 2 but was very uncommon in patients given 60 mg/m 2 . Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [see Adverse Reactions (6.1), Clinical Studies (14)]. Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [see Dosage and Administration (2.7), Adverse Reactions (6)] . 5.4 Enterocolitis and Neutropenic Colitis Enterocolitis and neutropenic colitis (typhlitis) have occurred in patients treated with DOCETAXEL INJECTION alone and in combination with other chemotherapeutic agents, despite the coadministration of G-CSF. Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis and neutropenic enterocolitis may develop at any time, and could lead to death as early as the first day of symptom onset. Monitor patients closely from onset of any symptoms of gastrointestinal toxicity. Inform patients to contact their healthcare provider with new, or worsening symptoms of gastrointestinal toxicity [see Dosage and Administration (2), Warnings and Precautions (5.3), Adverse Reactions (6.2)]. 5.5 Hypersensitivity Reactions Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the DOCETAXEL INJECTION infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with DOCETAXEL INJECTION [see Contraindications (4)]. Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of DOCETAXEL INJECTION therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a DOCETAXEL INJECTION infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of DOCETAXEL INJECTION [see Dosage and Administration (2.6)]. 5.6 Fluid Retention Severe fluid retention has been reported following docetaxel therapy. Patients should be premedicated with oral corticosteroids prior to each DOCETAXEL INJECTION administration to reduce the incidence and severity of fluid retention [see Dosage and Administration (2 .6) ] . Patients with preexisting effusions should be closely monitored from the first dose for the possible exacerbation of the…