HIGHLIGHTS OF PRESCRIBING INFORMATION ... - …

1 1 HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese HIGHLIGHTS do not include all the INFORMATION needed to use gemzar safely and effectively. See full PRESCRIBING INFORMATION for (gemcitabine) for injection, for intravenous useInitial Approval: 1996---------------------------RECENT MAJOR CHANGES--------------------------Warning s and Precautions,Hemolytic Uremic Syndrome ( ) 5/2019----------------------------INDICA TIONS AND USAGE--------------------------- gemzar 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.

2 ( ) 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 singleagent for the treatment of pancreatic cancer. ( )------------------------DOSAGE AND ADMINISTRATION-----------------------GEM ZARis for intravenous use only. OvarianCancer: 1000mg/m2over 30 minutes on Days 1 and 8 of each 21-day cycle.

3 ( ) Breast Cancer: 1250mg/m2over 30 minutes on Days 1 and 8 of each 21-day cycle. ( ) Non-Small Cell Lung Cancer: 1000mg/m2over 30 minutes on Days 1, 8, and 15 of each 28-day cycle or 1250mg/m2over 30 minutes on Days 1 and 8 of each 21-day cycle. ( ) PancreaticCancer: 1000mg/m2over 30 minutes once weekly for the first7 weeks, then one weekrest, then once weekly for 3 weeks of each 28-day cycle. ( )----------------------DOSAGE FORMS AND STRENGTHS---------------------For injection: 200 mg or 1 gram lyophilized powder in single-dose vialsfor reconstitution.

4 (3)-------------------------------CONTRA INDICATIONS----------------------------- -Patients with a known hypersensitivity to gemcitabine. (4)------------------------WARNINGS AND PRECAUTIONS----------------------- 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.( , ) Pulmonary Toxicity and Respiratory Failure: Discontinue GEMZARfor unexplained dyspnea or other evidence ofsevere pulmonary toxicity.

5 ( ) HemolyticUremic Syndrome (HUS): Monitor renal function prior to initiation and during treatment. DiscontinueGEMZARfor HUSor severe renal impairment. ( ) Hepatic Toxicity: Monitor hepatic function prior to initiation and duringtreatment. Discontinue GEMZARfor severe hepatic toxicity.( ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females and males of reproductive potential to use effective contraception. ( , ) Exacerbation of Radiation Therapy Toxicity: May cause severe and life-threatening toxicitywhen administered during or within 7 days of radiation therapy.

6 ( ) Capillary Leak Syndrome: Discontinue gemzar . ( ) Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue gemzar . ( )-------------------------------ADVERSE REACTIONS------------------------------T he most common adverse reactions for the singleagent ( 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. ( )To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or IN SPECIFIC POPULATIONS------------------------Lacta tion: Advise not to breastfeed.

7 ( )See 17 for PATIENT COUNSELING : 5/2019 FULL PRESCRIBING INFORMATION : CONTENTS*1 INDICATIONS AND Cell Lung Cancer2 DOSAGE AND Cell Lung Modifications for Non-Hematologic Adverse DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Toxicity and Respiratory of Radiation Therapy Leak Reversible Encephalopathy Syndrome6 ADVERSE Trials Experience8 USE IN SPECIFIC and Males of Reproductive Gender10 OVERDOSAGE11 DESCRIPTION12 CLINICAL of NONCLINICAL , Mutagenesis.

8 Impairment of Fertility14 CLINICAL Cell Lung Cancer15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full PRESCRIBING INFORMATION are not PRESCRIBING INFORMATION1 INDICATIONS AND CancerGEMZAR 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 CancerGEMZARin combination withpaclitaxel 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 Cell Lung CancerGEMZAR in combination with cisplatin is indicated for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer(NSCLC).

9 CancerGEMZARis indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. GEMZARis indicated for patients previously treated AND CancerRecommended Dose and ScheduleThe recommendeddosage of GEMZARis 1000mg/m2intravenously over 30minutes on Days1 and 8 of each 21-day cyclein combination with carboplatinAUC4 administered intravenously on Day 1 after to carboplatin PRESCRIBING INFORMATION for additional ModificationsRecommended gemzar dosage modifications for myelosuppression are describedin Tables 1 and 2[see Warnings and Precautions ( )].

10 Refer to the recommended dosage modifications for non-hematologic adverse reactions [see Dosage and Administration ( )].Table 1: Recommended Dosage Modificationsfor GEMZARfor Myelosuppression on Day of Treatment in OvarianCancerTreatment DayAbsolute NeutrophilCount(x 106/L)Platelet Count(x 106/L)DosageModificationDay 1 Greater than or equal to 1500 AndGreater than or equal to 100,000 NoneLess than 1500 OrLess than 100,000 Delay Treatment CycleDay 8 Greater than or equal to 1500 AndGreater than or equal to100,000 None1000to 1499Or75,000to 99,99950% of full doseLess than 1000 OrLess than 75,000 Hold3 Table 2.