openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
warnings and cautions
5 WARNINGS AND PRECAUTIONS • Schedule-Dependent Toxicity: Increased toxicity with infusion time greater than 60 minutes or dosing more frequently than once weekly. ( 5.1 ) • Myelosuppression: Monitor for myelosuppression prior to each cycle and reduce or withhold dose for severe myelosuppression. ( 5.2 ) • Severe Cutaneous Adverse Reactions (SCARs): Permanently discontinue Gemcitabine Injection if SCARs occur. ( 5.3 ) • Pulmonary Toxicity and Respiratory Failure: Discontinue Gemcitabine Injection for unexplained dyspnea or other evidence of severe pulmonary toxicity. ( 5.4 ) • Hemolytic Uremic Syndrome (HUS): Monitor renal function prior to initiation and during treatment. Discontinue Gemcitabine Injection for HUS or severe renal impairment. ( 5.5 ) • Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment. Discontinue Gemcitabine Injection for severe hepatic toxicity. ( 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females and males of reproductive potential to use effective contraception. ( 5.7 , 8.1 ) • Exacerbation of Radiation Therapy Toxicity: May cause severe and life-threatening toxicity when administered during or within 7 days of radiation therapy. ( 5.8 ) • Capillary Leak Syndrome: Discontinue Gemcitabine Injection. ( 5.9 ) • Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue Gemcitabine Injection. ( 5.10 ) 5.1 Schedule-Dependent Toxicity In clinical trials evaluating the maximum tolerated dose of gemcitabine, prolongation of the infusion time beyond 60 minutes or more frequent than weekly dosing resulted in an increased incidence of clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia. The half-life of gemcitabine is influenced by the length of the infusion [see Clinical Pharmacology (12.3) ] . Refer to the recommended Gemcitabine Injection dosage [see Dosage and Administration (2.1 , 2.2 , 2.3 , 2.4) ] . 5.2 Myelosuppression Myelosuppression manifested by neutropenia, thrombocytopenia, and anemia, occurs with gemcitabine as a single agent and the risks are increased when gemcitabine is combined with other cytotoxic drugs. In clinical trials, Grade 3 to 4 neutropenia, anemia, and thrombocytopenia occurred in 25%, 8%, and 5%, respectively of the 979 patients who received single agent gemcitabine. The frequencies of Grade 3 to 4 neutropenia, anemia, a...
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
adverse reactions
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 (5.6) ] • Exacerbation of Radiation Therapy Toxicity [see Warnings and Precautions (5.8) ] • Capillary Leak Syndrome [see Warnings and Precautions (5.9) ] • Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.10) ] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Single Agent The data described below reflect exposure to gemcitabine as a single agent administered at doses between 800 mg/m 2 to 1250 mg/m 2 intravenously over 30 minutes once weekly, in 979 patients with various malignancies. The most common (≥20%) adverse reactions of single agent gemcitabine are nausea/vomiting, anemia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), neutropenia, increased alkaline phosphatase, proteinuria, fever, hematuria, rash, thrombocytopenia, dyspnea, and edema. The most common (≥5%) Grade 3 or 4 adverse reactions were neutropenia, nausea/vomiting, increased ALT, increased alkaline phosphatase, anemia, increased AST, and thrombocytopenia. Approximately 10% of the 979 patients discontinued gemcitabine due to adverse reactions. Adverse reactions resulting in discontinuation of ge...
adverse reactions table
Table 5: Selected Adverse Reactions Occurring in ≥10% of Patients Receiving Single Agent GemcitabineGrade based on criteria from the World Health Organization (WHO).Adverse ReactionsFor approximately 60% of patients, non-laboratory adverse events were graded only if assessed to be possibly drug-related.GemcitabineN=699 to 974; all patients with laboratory or non-laboratory data.All Grades (%)Grade 3(%)Grade 4(%)Nausea and Vomiting69131Fever4120Rash30<10Dyspnea233<1Diarrhea1910Hemorrhage17<1<1Infection161<1Alopecia15<10Stomatitis11<10Somnolence11<1<1Paresthesias10<10