Important Safety Information for GEMZAR® (gemcitabine for injection)
Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.
Contraindication
Known hypersensitivity to GEMZAR.
Warnings and Precautions
Patients receiving therapy with GEMZAR should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.
Infusions of GEMZAR longer than 60 minutes or dosing more frequently than once weekly have been shown to increase toxicity.
GEMZAR can suppress bone marrow function, as manifested by leukopenia, thrombocytopenia, and anemia. Patients should be monitored for myelosuppression during therapy including a complete blood count with differential prior to each dose.
Pulmonary toxicity, sometimes fatal, has been reported. In cases of severe lung toxicity, GEMZAR therapy should be discontinued immediately and appropriate supportive care measures instituted.
Monitor renal and hepatic function prior to initiation of GEMZAR therapy and periodically thereafter. Use GEMZAR with caution in patients with renal impairment or hepatic impairment. Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of GEMZAR. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been reported. The majority of the cases of renal failure leading to death were due to HUS. Serious hepatotoxicity, including liver failure and death, has been reported in patients receiving GEMZAR alone or in combination with other potentially hepatotoxic drugs. Discontinue GEMZAR for HUS, or severe renal or hepatic toxicity.
GEMZAR can cause fetal harm. Advise women of potential risk to the fetus.
GEMZAR has radiosensitizing activity, and radiation recall reactions have been reported. The optimum regimen for safe administration of GEMZAR with therapeutic doses of radiation has not yet been determined in all tumor types.
Use in Specific Populations
GEMZAR is Pregnancy Category D. GEMZAR can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, GEMZAR is expected to result in adverse reproductive effects. It is not known whether GEMZAR is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and efficacy of GEMZAR in pediatric patients has not been established.
Use caution in patients with preexisting renal impairment or hepatic insufficiency. Administration of GEMZAR may exacerbate underlying hepatic insufficiency.
GEMZAR clearance is affected by age as well as gender.
Dose Modifications and Administration Guidelines
GEMZAR is for intravenous use only. Dosage adjustments for hematologic toxicity may be required. Dose modifications may be considered for severe nonhematologic toxicity. Modify or suspend therapy according to the Dosage and Administration guidelines in the full Prescribing Information.
Serum creatinine, potassium, calcium, and magnesium should be monitored during combination therapy with cisplatin. See the manufacturers’ prescribing information for more information on any drug indicated in combination with GEMZAR.
Abbreviated Adverse Reactions (% incidence) — 1st-line Advanced NSCLC
The most severe adverse reactions (grades 3/4, with incidence of 5% or greater) with GEMZAR plus cisplatin for the first-line treatment of patients with NSCLC in comparative trials of a 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and a 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were neutropenia (57 vs 4, 64 vs 76); thrombocytopenia (50 vs 4, 55 vs 13); leukopenia (46 vs 3, 29 vs 43); lymphocytopenia 28d (43 vs 17); anemia (25 vs 7, 22 vs 15); nausea/vomiting 21d (39 vs 26); nausea 28d (27 vs 21); vomiting 28d (23 vs 19); alopecia 21d (13 vs 51); neuromotor 28d (12 vs 3); dyspnea (7 vs 5, 1 vs 0); hypomagnesemia 28d (7 vs 2); neurohearing 28d (6 vs 6); creatinine elevation 28d (5 vs 3); and infection (5 vs 1, 4 vs 8).
The most common adverse reactions (all grades, with incidence of 20% or greater) of the 28-day regimen (GEMZAR plus cisplatin versus cisplatin alone) and the 21-day regimen (GEMZAR plus cisplatin versus etoposide plus cisplatin), respectively, were anemia (89 vs 67, 88 vs 77); neutropenia (79 vs 20, 88 vs 87); leukopenia (82 vs 25, 86 vs 87); thrombocytopenia (85 vs 13, 81 vs 45); lymphocytopenia 28d (75 vs 51); RBC transfusion (39 vs 13, 29 vs 21); platelet transfusions (21 vs 1, 3 vs 8); nausea 28d (93 vs 87); vomiting 28d (78 vs 71); nausea and vomiting 21d (96 vs 86); alopecia (53 vs 33, 77 vs 92); creatinine elevation (38 vs 31, 2 vs 2); paresthesias 21d (38 vs 16); neuromotor 28d (35 vs 15); hyperglycemia 28d (30 vs 23); hypomagnesemia 28d (30 vs 17); infection (18 vs 12, 28 vs 21); neurohearing 28d (25 vs 21); diarrhea (24 vs 13, 14 vs 13); proteinuria (23 vs 18, 12 vs 5); neurosensory 28d (23 vs 18); hematuria (15 vs 13, 22 vs 10); hepatic transaminase 28d (22 vs 10); and stomatitis (14 vs 5, 20 vs 18).
Abbreviated Adverse Reactions (% incidence) — Advanced Recurrent Ovarian Cancer
The most severe adverse reactions (grades 3/4, with incidence of 5% or greater) with GEMZAR plus carboplatin versus carboplatin alone, respectively, for the treatment of patients with advanced ovarian cancer were neutropenia (71 vs 12); leukopenia (53 vs 7); thrombocytopenia (35 vs 11); anemia (28 vs 11); constipation (7 vs 3); nausea (6 vs 3); and vomiting (6 vs 3).
The most common adverse reactions (all grades, with incidence of 20% or greater) in the same patient population were neutropenia (90 vs 58); anemia (86 vs 75); leukopenia (86 vs 70); thrombocytopenia (78 vs 57); RBC transfusion (38 vs 15); nausea (69 vs 61); alopecia (49 vs 17); vomiting (46 vs 36); constipation (42 vs 37); fatigue (40 vs 32); neuropathy-sensory (29 vs 27); diarrhea (25 vs 14); and stomatitis/pharyngitis (22 vs 13).
Abbreviated Adverse Reactions (% incidence) — 1st-line Metastatic Breast Cancer
The most severe adverse reactions (grades 3/4, with incidence of 5% or greater) with GEMZAR plus paclitaxel versus paclitaxel alone, respectively, for the treatment of patients with metastatic breast cancer were neutropenia (48 vs 11); leukopenia (11 vs 2); anemia (7 vs 4); thrombocytopenia (6 vs 2); alopecia (18 vs 22); fatigue (7 vs 2); ALT elevation (6 vs 1); and neuropathy-sensory (6 vs 3).
The most common adverse reactions (all grades, with incidence of 20% or greater) in the same patient population were anemia (69 vs 51); neutropenia (69 vs 31); thrombocytopenia (26 vs 7); leukopenia (21 vs 12); alopecia (90 vs 92); neuropathy-sensory (64 vs 58); nausea (50 vs 31); fatigue (40 vs 28); myalgia (33 vs 33); vomiting (29 vs 15); arthralgia (24 vs 22); and diarrhea (20 vs 13).
Abbreviated Adverse Reactions (% incidence) — 1st-line Advanced Pancreatic Cancer
The most severe adverse reactions (grades 3/4, with incidence of 5% or greater) in pancreatic cancer patients receiving single-agent GEMZAR were neutropenia (24), anemia (10), leukopenia (9), thrombocytopenia (8), alkaline phosphate elevation (20), AST elevation (17), nausea/vomiting (12), ALT elevation (11), and bilirubin elevation (8).
The most common adverse reactions (all grades, with incidence of 10% or greater) in the same patient population were anemia (73), leukopenia (64), neutropenia (61), thrombocytopenia (36), AST elevation (78), alkaline phosphate elevation (77), ALT elevation (72), nausea/vomiting (71), fever (38), proteinuria (32), diarrhea (30), rash (28), bilirubin elevation (26), hematuria (23), alopecia (16), BUN elevation (15), somnolence (11), dyspnea (10), infection (10), paresthesias (10), and stomatitis (10).
For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.
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