Gemcitabine

Gemcitabine Injection is a nucleoside metabolic inhibitor indicated: • in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. • in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. • in combination with cisplatin for the treatment of non-small cell lung cancer. • as a single agent for the treatment of pancreatic cancer.

Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary. Gemcitabine is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabine diphosphate inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate deoxynucleoside triphosphates for DNA synthesis, resulting in reductions in deoxynucleotide concentrations, including dCTP. Gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP by the action of the diphosphate enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation).

Gemcitabine Injection is for intravenous use only. • Ovarian Cancer: 1000 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. • Breast Cancer: 1250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. • Non-Small Cell Lung Cancer: 1000 mg/m 2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle or 1250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. • Pancreatic Cancer: 1000 mg/m 2 over 30 minutes once weekly for the first 7 weeks, then one-week rest, then once weekly for 3 weeks of each 28-day cycle.

Gemcitabine Injection is contraindicated in patients with a known hypersensitivity to gemcitabine. Reactions include anaphylaxis. Patients with a known hypersensitivity to gemcitabine.

• Schedule-Dependent Toxicity: Increased toxicity with infusion time greater than 60 minutes or dosing more frequently than once weekly. • Myelosuppression: Monitor for myelosuppression prior to each cycle and reduce or withhold dose for severe myelosuppression. • Severe Cutaneous Adverse Reactions (SCARs): Permanently discontinue Gemcitabine Injection if SCARs occur. • Pulmonary Toxicity and Respiratory Failure: Discontinue Gemcitabine Injection for unexplained dyspnea or other evidence of severe pulmonary toxicity. • Hemolytic Uremic Syndrome (HUS): Monitor renal function prior to initiation and during treatment. Discontinue Gemcitabine Injection for HUS or severe renal impairment. • Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment. Discontinue Gemcitabine Injection for severe hepatic toxicity. • Embryo-Fetal Toxicity: Can cause fetal harm.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity • Schedule-Dependent Toxicity • Myelosuppression • Severe Cutaneous Adverse Reactions • Pulmonary Toxicity and Respiratory Failure • Hemolytic Uremic Syndrome • Hepatic Toxicity • Exacerbation of Radiation Therapy Toxicity • Capillary Leak Syndrome • Posterior Reversible Encephalopathy Syndrome The most common adverse reactions for the single agent (≥20%) are nausea/vomiting, anemia, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), neutropenia, increased alkaline phosphatase, proteinuria, fever, hematuria, rash, thrombocytopenia, dyspnea, and edema.

Store at 2° to 8°C (36° to 46°F). Do not freeze.