Reference ID: 3101735 - Food and Drug …

1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Docetaxel Injection safely and effectively. See full prescribing information for Docetaxel Injection. Docetaxel Injection, Solution for Intravenous Infusion Initial Approval: 1996 WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION See full prescribing information for complete boxed warning Treatment-related mortality increases with abnormal liver function, at higher doses, and in patients with NSCLC and prior platinum-based therapy receiving docetaxel at 100 mg/m2 ( ) Should not be given if bilirubin > ULN, or if AST and/or ALT > x ULN concomitant with alkaline phosphatase > x ULN.

2 LFT elevations increase risk of severe or life-threatening complications. Obtain LFTs before each treatment cycle ( ) Should not be given if neutrophil counts are < 1500 cells/mm3. Obtain frequent blood counts to monitor for neutropenia (4) Severe hypersensitivity, including very rare fatal anaphylaxis, has been reported in patients who received dexamethasone premedication. Severe reactions require immediate discontinuation of Docetaxel Injection and administration of appropriate therapy ( ) Contraindicated if history of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80 (4) Severe fluid retention may occur despite dexamethasone ( ) ---------------------------------------- -------R E C E N T M A J O R C H A N G E -------------------------- - Preparation and Administration ( ) 03/2012 ---------------------------------------- --I N D I C A T I O N S A N D U S A G E ------------------------Docetaxel Injection is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure.

3 And with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ( ) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC ( ) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer ( ) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction ( ) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN ( ) ----------------------------D O S A G E A N D A D M I N I S T R A T I O N ------------------------------- Administer in a facility equipped to manage possible complications ( , anaphylaxis).

4 Administer intravenously over 1 hr every 3 weeks. PVC equipment is not recommended. BC locally advanced or metastatic: 60 mg/m2 to 100 mg/m2 single agent ( ) BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles ( ) NSCLC: after platinum therapy failure: 75 mg/m2 single agent ( ) NSCLC: chemotherapy-naive: 75 mg/m2 followed by cisplatin 75 mg/m2 ( ) HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously ( ) GC: 75 mg/m2 followed by cisplatin 75 mg/m2 (both on day 1 only) followed by fluorouracil 750 mg/m2 per day as a 24-hr intravenous infusion (days 1-5), starting at end of cisplatin infusion ( ) SCCHN: 75 mg/m2 followed by cisplatin 75 mg/m2 intravenously (day 1), followed by fluorouracil 750 mg/m2 per day as a 24-hr intravenous infusion (days 1-5), starting at end of cisplatin infusion.

5 For 4 cycles ( ) SCCHN: 75 mg/m2 followed by cisplatin 100 mg/m2 intravenously (day 1), followed by fluorouracil 1000 mg/m2 per day as a 24-hr intravenous infusion (days 1-4); for 3 cycles ( ) For all patients: Premedicate with oral corticosteroids ( ) Adjust dose as needed ( ) -----------------------------D O S A G E F O R M S A N D S T R E N G T H S --------------------- Multiple dose vial 20 mg/2 mL, 80 mg/8 mL and 160 mg/16 mL (3) ---------------------------------------- --C O N T R A I N D I C A T I O N S ---------------------------------- Hypersensitivity to docetaxel or polysorbate 80 (4) Neutrophil counts of <1500 cells/mm3 (4) -------------------------------WARNINGS AND PRECAUTIONS----- -------------------- Acute myeloid leukemia: In patients who received docetaxel, doxorubicin and cyclophosphamide, monitor for delayed myelodysplasia or myeloid leukemia ( ) Cutaneous reactions.

6 Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe skin toxicity may require dose adjustment ( ) Neurologic reactions: Reactions including paresthesia, dysesthesia, and pain may occur. Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. ( ) Asthenia: Severe asthenia may occur and may require treatment discontinuation. ( ) Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women of childbearing potential should be advised not to become pregnant when receiving Docetaxel Injection ( , ) ---------------------------------------- ---------- A D V E R S E R E A C T I O N S ------------------------ Most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, myalgia (6) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc.

7 , at 1-800-525-8747 or FDA at 1-800-FDA-1088 or ---------------------------------------- - D R U G I N T E R A C T I O N S ---------------------------------- Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (7) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling Reference ID: 3101735 03/2012 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING 1 INDICATIONS AND USAGE Breast Cancer Non-Small Cell Lung Cancer Prostate Cancer Gastric Adenocarcinoma Head and Neck Cancer 2 DOSAGE AND ADMINISTRATION Breast Cancer Non-Small Cell Lung Cancer Prostate Cancer Gastric Adenocarcinoma Head and Neck Cancer Premedication Regimen Dosage Adjustments During Treatment Administration Precautions Preparation and Administration Stability 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS Toxic Deaths Hepatic Impairment Hematologic Effects Hypersensitivity Reactions Fluid Retention Acute Myeloid Leukemia Cutaneous reaction Neurologic Reactions Asthenia Use in Pregnancy 6 ADVERSE REACTIONS Clinical Trials Experience Post Marketing

8 Experiences 7 drug INTERACTIONS 8 USE IN SPECIFIC POPULATIONS Pregnancy Nursing Mothers Pediatric Use Geriatric Use Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY Mechanism of Action Human Pharmacokinetics 13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES Locally Advanced or Metastatic Breast Cancer Adjuvant Treatment of Breast Cancer Non-Small Cell Lung Cancer (NSCLC) Hormone Refractory Prostate Cancer Gastric Adenocarcinoma Head and Neck Cancer 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Storage Handling and Disposal 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing information are not listed Reference ID: 3101735 FULL PRESCRIBING INFORMATION WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, and FLUID RETENTION The incidence of treatment-related mortality associated with docetaxel therapy 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 docetaxel as a single agent at a dose of 100 mg/m2 [see Warning and Precautions ( )].

9 Docetaxel Injection should not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT > x ULN concomitant with alkaline phosphatase > x ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase > x ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death. Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of Docetaxel Injection therapy [see Warning and Precautions ( )].

10 Docetaxel Injection therapy should not be given to patients with neutrophil counts of <1500 cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood cell counts should be performed on all patients receiving Docetaxel Injection [see Warning and Precautions ( )]. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received a 3-day dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and administration of appropriate therapy [see Warning and Precautions ( )]. Docetaxel Injection must not be given to patients who have a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80 [see Contraindications (4)].