GEMZAR - gemcitabine hydrochloride injection, powder, lyophilized, for solution
Eli Lilly and Company
1 INDICATIONS AND USAGE
1.1 Ovarian Cancer
Gemzar in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.
1.2 Breast Cancer
Gemzar in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.
1.3 Non-Small Cell Lung Cancer
Gemzar is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.
1.4 Pancreatic Cancer
Gemzar is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemzar is indicated for patients previously treated with 5-FU.
2 DOSAGE AND ADMINISTRATION
2.1 Ovarian Cancer
Recommended Dose and Schedule
The recommended dose of Gemzar is 1000 mg/m2 as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, in combination with carboplatin AUC 4 intravenously after Gemzar administration on Day 1 of each 21-day cycle. Refer to carboplatin prescribing information for additional information.
Dose Modifications
Recommended Gemzar dose modifications for myelosuppression are described in Table 1 and Table 2 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions.
DOSAGE FORMS AND STRENGTHS
Gemzar (gemcitabine for injection USP) is a white to off-white lyophilized powder available in sterile single-use vials containing 200 mg or 1 g gemcitabine.
DESCRIPTION
Gemzar (gemcitabine for injection, USP) is a nucleoside metabolic inhibitor that exhibits antitumor activity. Gemcitabine HCl is 2?-deoxy-2?,2?-difluorocytidine monohydrochloride (?-isomer).
The empirical formula for gemcitabine HCl is C9 H11 F2 N3 O4 � HCl. It has a molecular weight of 299.66.
Gemcitabine HCl is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.
Gemzar is supplied in a sterile form for intravenous use only. Vials of Gemzar contain either 200 mg or 1 g of gemcitabine HCl (expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
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). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands, which eventually results in the initiation of apoptotic cell death.
