2 DOSAGE AND ADMINISTRATION Gemcitabine for 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 (2.4) 2.1Ovarian Cancer Recommended Dose and Schedule The recommended dose of gemcitabine for injection is 1000 mg/m 2 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 gemcitabine for injection administration on Day 1 of each 21-day cycle. Refer to carboplatin prescribing information for additional information. Dose Modifications Recommended gemcitabine for injection dose modifications for myelosuppression are described 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. Table 1: Dosage Reduction Guidelines for Gemcitabine for Injection for Myelosuppression on Day of Treatment in Ovarian Cancer Treatment Day Absolute granulocyte count (x 10 6 /L) Platelet count (x 10 6 /L) % of full dose Day 1 ≥1500 and ≥100,000 100% <1500 or <100,000 Delay Treatment Cycle Day 8 ≥1500 and ≥100,000 100 1000 to 1499 or 75,000 to 99,999 50 <1000 or <75,000 Hold Table 2: Gemcitabine for Injection Dose Modification for Myelosuppression in Previous Cycle In Ovarian Cancer Occurrence Myelosuppression During Treatment Cycle Dose Modification Initial Occurrence Absolute granulocyte count less than 500 x 10 6 /L for more than 5 days Absolute granulocyte count less than 100 x 10 6 /L for more than 3 days Febrile neutropenia Platelets less than 25,000x10 6 /L Cycle delay of more than one week due to toxicity Permanently reduce gemcitabine for injection to 800 mg/m 2 on Days 1 and 8 Subsequent Occurrence If any of the above toxicities occur after the initial dose reduction Permanently reduce gemcitabine for injection dose to 800 mg/m 2 on Day 1 only 2.2Breast Cancer Recommended Dose and Schedule The recommended dose of gemcitabine for injection is 1250 mg/m 2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle that includes paclitaxel. Paclitaxel should be administered at 175 mg/m 2 on Day 1 as a 3 hour intravenous infusion before gemcitabine for injection administration. Dose Modifications Recommended dose modifications for gemcitabine for injection for myelosuppression are described in Table 3 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions. Table 3: Recommended Dose Reductions for Gemcitabine for Injection for Myelosuppression on Day of Treatment in Breast Cancer Treatment Day Absolute granulocyte count (x 10 6 /L) Platelet count (x 10 6 /L) % of full dose Day 1 ≥1500 and ≥100,000 100% less than 1500 or less than 100,000 Hold Day 8 ≥1200 and >75,000 100% 1000 to 1199 or 50,000 to 75,000 75% 700 to 999 and ≥50,000 50% <700 or <50,000 Hold 2.3Non-Small Cell Lung Cancer Recommended Dose and Schedule Every 4-week schedule The recommended dose of gemcitabine for injection is 1000 mg/m 2 intravenously over 30 minutes on Days 1, 8, and 15 in combination with cisplatin therapy. Administer cisplatin intravenously at 100 mg/m 2 on Day 1 after the infusion of gemcitabine for injection. Every 3-week schedule The recommended dose of gemcitabine for injection is 1250 mg/m 2 intravenously over 30 minutes on Days 1 and 8 in combination with cisplatin therapy. Administer cisplatin intravenously at 100 mg/m 2 on Day 1 after the infusion of gemcitabine for injection. Dose Modifications Recommended dose modifications for gemcitabine for injection myelosuppression are described in Table 4 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for gemcitabine for injection recommendations for non-hematologic adverse reactions. 2.4Pancreatic Cancer Recommended Dose and Schedule The recommended dose of gemcitabine for injection is 1000 mg/m 2 over 30 minutes intravenously. The recommended treatment schedule • Weeks 1 to 8: weekly dosing for the first 7 weeks followed by one week rest. • After week 8: weekly dosing on Days 1, 8, and 15 of 28-day cycles. Dose Modifications Recommended dose modifications for gemcitabine for injection for myelosuppression are described in Table 4 [see Warnings and Precautions (5.2)]. Refer to Dosage and Administration (2.5) for recommendations for non-hematologic adverse reactions. Patients receiving gemcitabine for injection should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 4. Table 4: Recommended Dose Reductions for Gemcitabine for Injection for Myelosuppression in Pancreatic Cancer and Non-Small Cell Lung Cancer Absolute granulocyte count (x 10 6 /L) Platelet count (x 10 6 /L) % of full dose ≥1000 And ≥100,000 100 500 to 999 Or 50,000 to 99,999 75 <500 Or <50,000 Hold 2.5Dose Modifications for Non-Hematologic Adverse Reactions Permanently discontinue gemcitabine for injection for any of the following • Unexplained dyspnea or other evidence of severe pulmonary toxicity • Severe hepatic toxicity • Hemolytic-Uremic Syndrome • Capillary Leak Syndrome • Posterior reversible encephalopathy syndrome Withhold gemcitabine for injection or reduce dose by 50% for other severe (Grade 3 or 4) non-hematological toxicity until resolved. No dose modifications are recommended for alopecia, nausea, or vomiting. 2.6Preparation and Administration Precautions Exercise caution and wear gloves when preparing gemcitabine for injection solutions. Immediately wash the skin thoroughly or rinse the mucosa with copious amounts of water if gemcitabine for injection contacts the skin or mucus membranes. Death has occurred in animal studies due to dermal absorption. For further guidance on handling gemcitabine for injection go to “OSHA Hazardous Drugs” (refer to antineoplastic weblinks including OSHA Technical Manual) at OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html 2.7Preparation for Intravenous Infusion Administration Reconstitute the vials with 0.9% Sodium Chloride Injection without preservatives. Add 5 mL to the 200-mg vial or 25 mL to the 1-g vial. These dilutions each yield a gemcitabine for injection concentration of 38 mg/mL. Complete withdrawal of the vial contents will provide 200 mg or 1 g of gemcitabine for injection. Prior to administration the appropriate amount of drug must be diluted with 0.9% Sodium Chloride Injection. Final concentrations may be as low as 0.1 mg/mL. Reconstituted gemcitabine for injection is a clear, colorless to light straw-colored solution. Inspect visually prior to administration and discard for particulate matter or discoloration. Gemcitabine for injection solutions are stable for 24 hours at controlled room temperature of 20° to 25°C (68° to 77°F). Do not refrigerate as crystallization can occur. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.