Warnings and Precautions (5.9, 5.12)      07/2014

Docetaxel Injection is a microtubule inhibitor indicated for:

• Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1)

• 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 (1.2)

• Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3)

• Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4)

• Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5)

Administer in a facility equipped to manage possible complications (e.g., anaphylaxis).Administer intravenously over 1 hr every 3 weeks. PVC equipment is not recommended. For One-vial formulation, use only a 21 gauge needle to withdraw Docetaxel Injection Concentrate from the vial.

• BC: locally advanced or metastatic: 60 mg/m2 to 100 mg/m2 single agent (2.1)
• BC adjuvant: 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 cycles (2.1)
• NSCLC: after platinum therapy failure: 75 mg/m2 single agent (2.2)
• NSCLC: chemotherapy-naive: 75 mg/m2 followed by cisplatin 75 mg/m2 (2.2)
• HRPC: 75 mg/m2 with 5 mg prednisone twice a day continuously (2.3)
• 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 to 5), starting at end of cisplatin infusion (2.4)
• 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 to 5), starting at end of cisplatin infusion; for 4 cycles (2.5)
• 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 to 4); for 3 cycles (2.5)

For all patients:

• Premedicate with oral corticosteroids (2.6)
• Adjust dose as needed (2.7)

• 80 mg/2 mL and Diluent for Docetaxel Injection 80 mg,
• 20 mg/0.5 mL and Diluent for Docetaxel Injection 20 mg,
• One vial Docetaxel Injection Concentrate: Single use and Multi use vials
  160 mg/8 mL, 80 mg/4 mL and 20 mg/mL (3)

• Acute myeloid leukemia: In patients who received docetaxel, doxorubicin and cyclophosphamide, monitor for delayed myelodysplasia or myeloid leukemia (5.6)
• Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe skin toxicity may require dose adjustment (5.7)
• Neurologic reactions: Reactions including. paresthesia, dysesthesia, and pain may occur. Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. (5.8)
• Eye disorders: Cystoid macular edema (CME) has been reported and requires treatment discontinuation. (5.9)
• Asthenia: Severe asthenia may occur and may require treatment discontinuation. (5.10)
• 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 (5.11, 8.1)
• 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. (5.12)

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 Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

• Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (7)