Overview
11 DESCRIPTION Gemcitabine is a nucleoside metabolic inhibitor. The chemical name of gemcitabine HCl is 2´-deoxy-2´,2´-difluorocytidine monohydrochloride (β-isomer). The structural formula is as follows: Gemcitabine HCl, USP is a white to off-white solid with a molecular formula of C 9 H 11 F 2 N 3 O 4 • HCl and a molecular weight of 299.66 g/mol.
Mechanism of Action
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).
Indications
- 1 INDICATIONS AND USAGE 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. ( 1.1 ) • 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. ( 1.2 ) • in combination with cisplatin for the treatment of non-small cell lung cancer. ( 1.
Common Doses
- 1000 mg
- 1250 mg
- 800 mg
- 175 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) • Breast Cancer: 1250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.2 ) • 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. ( 2.3 ) • 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. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Gemcitabine Injection is contraindicated in patients with a known hypersensitivity to gemcitabine. Reactions include anaphylaxis [see Adverse Reactions (6.1) ] . Patients with a known hypersensitivity to gemcitabine. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity [see Contraindications (4) ] • Schedule-Dependent Toxicity [see Warnings and Precautions (5.1) ] • Myelosuppression [see Warnings and Precautions (5.2) ] • Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] • Pulmonary Toxicity and Respiratory Failure [see Warnings and Precautions (5.4) ] • Hemolytic Uremic Syndrome [see Warnings and Precautions (5.5) ] • Hepatic Toxicity [see Warnings and Precautions (5.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.