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TAXOTERE (Docetaxel) Injection, for Intravenous Use Cisplatin Infusion; for 4 Cycles (2.5) Initial U.S

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TAXOTERE (Docetaxel) Injection, for Intravenous Use Cisplatin Infusion; for 4 Cycles (2.5) Initial U.S HIGHLIGHTS OF PRESCRIBING INFORMATION • GC: 75 mg/m2 followed by cisplatin 75 mg/m2 (both on day 1 only) These highlights do not include all the information needed to use followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1-5), TAXOTERE safely and effectively. See full prescribing information for starting at end of cisplatin infusion (2.4) TAXOTERE. • SCCHN: 75 mg/m2 followed by cisplatin 75 mg/m2 IV (day 1), followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1-5), starting at end of TAXOTERE (docetaxel) injection, for intravenous use cisplatin infusion; for 4 cycles (2.5) Initial U.S. Approval: 1996 • SCCHN: 75 mg/m2 followed by cisplatin 100 mg/m2 IV (day 1), followed WARNING: TOXIC DEATHS, HEPATOTOXICITY, by fluorouracil 1000 mg/m2 per day as a 24-hr IV (days 1-4); for 3 cycles NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID (2.5) RETENTION For all patients: See full prescribing information for complete boxed warning. • Premedicate with oral corticosteroids (2.6) • Treatment-related mortality increases with abnormal liver function, • Adjust dose as needed (2.7) at higher doses, and in patients with NSCLC and prior platinum- ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ based therapy receiving TAXOTERE at 100 mg/m2 (5.1) • Injection: One-vial TAXOTERE: Single-dose vials 20 mg/mL and • Avoid use of TAXOTERE if bilirubin > ULN, or if AST and/or 80 mg/4 mL (3) ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. -------------------------------CONTRAINDICATIONS-----------------------------­ LFT elevations increase risk of severe or life-threatening • Hypersensitivity to docetaxel or polysorbate 80 (4) complications. Obtain LFTs before each treatment cycle (5.2) 3 • Neutrophil counts of <1500 cells/mm (4) • Do not administer TAXOTERE to patients with neutrophil counts <1500 cells/mm3. Obtain frequent blood counts to monitor for -----------------------WARNINGS AND PRECAUTIONS-----------------------­ neutropenia (4, 5.3) • Second primary malignancies: In patients treated with TAXOTERE- containing regimens, monitor for delayed AML, MDS, NHL, and renal • Severe hypersensitivity, including fatal anaphylaxis, has been cancer. (5.7) reported in patients who received dexamethasone premedication. • Cutaneous reactions: Reactions including erythema of the extremities with Severe reactions require immediate discontinuation of TAXOTERE edema followed by desquamation may occur. Severe cutaneous adverse and administration of appropriate therapy (5.5) reactions have been reported. Severe skin toxicity may require dose • Contraindicated if history of severe hypersensitivity reactions to adjustment or permanent treatment discontinuation. (5.8) TAXOTERE or to drugs formulated with polysorbate 80 (4) • Neurologic reactions: Reactions including paresthesia, dysesthesia, and • Severe fluid retention may occur despite dexamethasone (5.6) pain may occur. Severe neurosensory symptoms require dose adjustment or ----------------------------RECENT MAJOR CHANGES-------------------------­ discontinuation if persistent. (5.9) Warnings and Precautions (5.7, 5.12) 06/2019 • Eye disorders: Cystoid macular edema (CME) has been reported and Warnings and Precautions (5.8) 12/2019 requires treatment discontinuation. (5.10) Warnings and Precautions (5.14) 05/2020 • Asthenia: Severe asthenia may occur and may require treatment ----------------------------INDICATIONS AND USAGE--------------------------­ discontinuation. (5.11) TAXOTERE is a microtubule inhibitor indicated for: • Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the • Breast Cancer (BC): single agent for locally advanced or metastatic BC potential risk to a fetus and to use effective contraception. (5.12, 8.1, 8.3) after chemotherapy failure; and with doxorubicin and cyclophosphamide as • Alcohol content: The alcohol content in a dose of TAXOTERE Injection adjuvant treatment of operable node-positive BC (1.1) may affect the central nervous system. This may include impairment of a • Non-small Cell Lung Cancer (NSCLC): single agent for locally advanced patient’s ability to drive or use machines immediately after infusion. (5.13) or metastatic NSCLC after platinum therapy failure; and with cisplatin for • Tumor lysis syndrome: Tumor lysis syndrome has been reported. Patients unresectable, locally advanced or metastatic untreated NSCLC (1.2) at risk should be well hydrated and closely monitored during treatment. • Castration-Resistant Prostate Cancer (CRPC): with prednisone in (5.14) metastatic castration-resistant prostate cancer (1.3) ------------------------------ADVERSE REACTIONS------------------------------­ • Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for Most common adverse reactions across all TAXOTERE indications are untreated, advanced GC, including the gastroesophageal junction (1.4) infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, • Squamous Cell Carcinoma of the Head and Neck (SCCHN): with thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, cisplatin and fluorouracil for induction treatment of locally advanced nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, SCCHN (1.5) mucositis, alopecia, skin reactions, and myalgia. (6) ----------------------DOSAGE AND ADMINISTRATION----------------------­ To report SUSPECTED ADVERSE REACTIONS, contact sanofi­ Administer in a facility equipped to manage possible complications (e.g., aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or anaphylaxis). Administer intravenously (IV) over 1 hr every 3 weeks. PVC www.fda.gov/medwatch. equipment is not recommended. Use only a 21 gauge needle to withdraw ------------------------------DRUG INTERACTIONS------------------------------­ TAXOTERE from the vial. • Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter • BC locally advanced or metastatic: 60 mg/m2 to 100 mg/m2 single agent docetaxel metabolism. (7) (2.1) • BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 -----------------------USE IN SPECIFIC POPULATIONS-----------------------­ and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (2.1) • Lactation: Advise women not to breastfeed. (8.2) • NSCLC: after platinum therapy failure: 75 mg/m2 single agent (2.2) • Females and Males of Reproductive Potential: Verify pregnancy status of • NSCLC: chemotherapy naive: 75 mg/m2 followed by cisplatin 75 mg/m2 females prior to initiation of TAXOTERE. (8.3) (2.2) 2 See 17 for PATIENT COUNSELING INFORMATION and FDA- • HRPC: 75 mg/m with 5 mg prednisone twice a day continuously (2.3) approved patient labeling. Revised: 05/2020 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, 2.2 Non-small Cell Lung Cancer HYPERSENSITIVITY REACTIONS, and FLUID RETENTION 2.3 Prostate Cancer 1 INDICATIONS AND USAGE 2.4 Gastric Adenocarcinoma 1.1 Breast Cancer 2.5 Head and Neck Cancer 1.2 Non-small Cell Lung Cancer 2.6 Premedication Regimen 1.3 Prostate Cancer 2.7 Dosage Adjustments during Treatment 1.4 Gastric Adenocarcinoma 2.8 Administration Precautions 1.5 Head and Neck Cancer 2.9 Preparation and Administration 2 DOSAGE AND ADMINISTRATION 2.10 Stability 2.1 Breast Cancer 3 DOSAGE FORMS AND STRENGTHS Reference ID: 4609125 4 CONTRAINDICATIONS 8.5 Geriatric Use 5 WARNINGS AND PRECAUTIONS 8.6 Hepatic Impairment 5.1 Toxic Deaths 10 OVERDOSAGE 5.2 Hepatic Impairment 11 DESCRIPTION 5.3 Hematologic Effects 12 CLINICAL PHARMACOLOGY 5.4 Enterocolitis and Neutropenic Colitis 12.1 Mechanism of Action 5.5 Hypersensitivity Reactions 12.3 Pharmacokinetics 5.6 Fluid Retention 13 NONCLINICAL TOXICOLOGY 5.7 Second Primary Malignancies 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.8 Cutaneous Reactions 14 CLINICAL STUDIES 5.9 Neurologic Reactions 14.1 Locally Advanced or Metastatic Breast Cancer 5.10 Eye Disorders 14.2 Adjuvant Treatment of Breast Cancer 5.11 Asthenia 14.3 Non-small Cell Lung Cancer (NSCLC) 5.12 Embryo-Fetal Toxicity 14.4 Castration-Resistant Prostate Cancer 5.13 Alcohol Content 14.5 Gastric Adenocarcinoma 5.14 Tumor Lysis Syndrome 14.6 Head and Neck Cancer 6 ADVERSE REACTIONS 15 REFERENCES 6.1 Clinical Trials Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 6.2 Postmarketing Experience 16.1 How Supplied 7 DRUG INTERACTIONS 16.2 Storage 8 USE IN SPECIFIC POPULATIONS 16.3 Handling and Disposal 8.1 Pregnancy 17 PATIENT COUNSELING INFORMATION 8.2 Lactation 8.3 Females and Males of Reproductive Potential *Sections or subsections omitted from the full prescribing information are not 8.4 Pediatric Use listed. 2 Reference ID: 4609125 FULL PRESCRIBING INFORMATION WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION Treatment-related mortality associated with TAXOTERE is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non- small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive TAXOTERE as a single agent at a dose of 100 mg/m2 [see Warnings and Precautions (5.1)]. Avoid the use of TAXOTERE 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. 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,
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