The following serious adverse reactions are discussed in greater detail in another section of the label

• Schedule-Dependent Toxicity [see WARNINGS AND PRECAUTIONS]
• Myelosuppression [see WARNINGS AND PRECAUTIONS]
• Pulmonary Toxicity and Respiratory Failure [see WARNINGS AND PRECAUTIONS]
• Hemolytic Uremic Syndrome [see WARNINGS AND PRECAUTIONS]
• Hepatic Toxicity [see WARNINGS AND PRECAUTIONS]
• Embryo-fetal Toxicity [see WARNINGS AND PRECAUTIONS, Use In Specific Populations, and Nonclinical Toxicology]
• Exacerbation of Radiation Toxicity [see WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]

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 clinical practice.

Single-Agent Use:

The data described below reflect exposure to Gemzar as a single agent administered at doses between 800 mg/m² to 1250 mg/m² over 30 minutes intravenously, once weekly, in 979 patients with a variety of malignancies. The most common ( ≥ 20%) adverse reactions of single-agent Gemzar are nausea/vomiting, anemia, increased ALT, increased 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, increase alkaline phosphatase, anemia, increased AST, and thrombocytopenia. Approximately 10% of the 979 patients discontinued Gemzar due to adverse reactions. Adverse reactions resulting in discontinuation of Gemzar in 2% of 979 patients were cardiovascular adverse events (myocardial infarction, cerebrovascular accident, arrhythmia, and hypertension) and adverse reactions resulting in discontinuation of Gemzar in less than 1% of the 979 patients were anemia, thrombocytopenia, hepatic dysfunction, renal dysfunction, nausea/vomiting, fever, rash, dyspnea, hemorrhage, infection, stomatitis, somnolence, flu-like syndrome, and edema.

Table 5 presents the incidence of adverse reactions reported in 979 patients with various malignancies receiving single-agent Gemzar across 5 clinical trials. Table 5 includes all clinical adverse reactions, reported in at least 10% of patients. A listing of clinically significant adverse reactions is provided following the table.

Table 5: Selected Per-Patient Incidence of Adverse Events in Patients Receiving Single-Agent Gemzar^a

• Transfusion requirements — Red blood cell transfusions (19%); platelet transfusions ( < 1%)
• Fever — Fever occurred in the absence of clinical infection and frequently in combination with other flu-like symptoms.
• Pulmonary — Dyspnea unrelated to underlying disease and sometimes accompanied by bronchospasm.
• Edema — Edema (13%), peripheral edema (20%), and generalized edema ( < 1%); < 1% of patients. discontinued Gemzar due to edema.
• Flu-like Symptoms — Characterized by fever, asthenia, anorexia, headache, cough, chills, myalgia, asthenia insomnia, rhinitis, sweating, and/or malaise (19%); < 1% of patients discontinued Gemzar due to flu-like symptoms
• Infection — Sepsis ( < 1%)
• Extravasation — Injection-site reactions (4%)
• Allergic — Bronchospasm ( < 2%); anaphylactoid reactions [see CONTRAINDICATIONS].

Non-Small Cell Lung Cancer

Table 6 presents the incidence of selected adverse reactions, occurring in ≥ 10% of Gemzar-treated patients and at a higher incidence in the Gemzar plus cisplatin arm, reported in a randomized trial of Gemzar plus cisplatin (n=262) administered in 28-day cycles as compared to cisplatin alone (n=260) in patients receiving first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) [see Clinical Studies].

Patients randomized to Gemzar plus cisplatin received a median of 4 cycles of treatment and those randomized to cisplatin received a median of 2 cycles of treatment. In this trial, the requirement for dose adjustments ( > 90% versus 16%), discontinuation of treatment for adverse reactions (15% versus 8%), and the proportion of patients hospitalized (36% versus 23%) were all higher for patients receiving Gemzar plus cisplatin arm compared to those receiving cisplatin alone. The incidence of febrile neutropenia (9/262 versus 2/260), sepsis (4% versus 1%), Grade 3 cardiac dysrhythmias (3% versus < 1%) were all higher in the Gemzar plus cisplatin arm compared to the cisplatin alone arm. The two-drug combination was more myelosuppressive with 4 (1.5%) possibly treatment-related deaths, including 3 resulting from myelosuppression with infection and one case of renal failure associated with pancytopenia and infection. No deaths due to treatment were reported on the cisplatin arm.

Table 6: Per-Patient Incidence of Selected Adverse Reactions from Randomized Trial of Gemzar plus Cisplatin versus Single-Agent Cisplatin in Patients with NSCLC Occurring at Higher Incidence in Gemzar-Treated Patients [Between Arm Difference of ≥ 5% (All Grades) or ≥ 2% (Grades 3-4)]^a

Table 7 presents the incidence of selected adverse reactions, occurring in ≥ 10% of Gemzar-treated patients and at a higher incidence in the Gemzar plus cisplatin arm, reported in a randomized trial of Gemzar plus cisplatin (n=69) administered in 21-day cycles as compared to etoposide plus cisplatin alone (n=66) in patients receiving first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) [see Clinical Studies]. A listing of clinically significant adverse reactions is provided following the table.

Patients in the Gemzar cisplatin (GC) arm received a median of 5 cycles and those in the etoposide/cisplatin (EC) arm received a median of 4 cycles. The majority of patients receiving more than one cycle of treatment required dose adjustments; 81% in the (GC) arm and 68% in the (EC) arm. The incidence of hospitalizations for treatment-related adverse events was 22% (GC) and 27% in the (EC) arm. The proportion of discontinuation of treatment for treatment-related adverse reactions was higher for patients in the (GC) arm (14% versus 8%). The proportion of patients hospitalized for febrile neutropenia was lower in the (GC) arm (7% versus 12%). There was one death attributed to treatment, a patient with febrile neutropenia and renal failure, which occurred in the Gemzar/cisplatin arm.

Table 7: Per-Patient Incidence of Selected Adverse Reactions in Randomized Trial of Gemzar plus Cisplatin versus Etoposide plus Cisplatin in Patients with NSCLC^a

• Flu-like syndrome: 3% in the Gemzar/cisplatin arm versus none in the etoposide/cisplatin arm.
• Edema: 12% in the Gemzar/cisplatin arm versus 2% in the etoposide/cisplatin arm.

Breast Cancer

Table 8 presents the incidence of selected adverse reactions, occurring in ≥ 10% of Gemzar-treated patients and at a higher incidence in the Gemzar plus paclitaxel arm, reported in a randomized trial of Gemzar plus paclitaxel (n=262) compared to paclitaxel alone (n=259) for the first-line treatment of metastatic breast cancer (MBC) in women who received anthracycline-containing chemotherapy in the adjuvant/neo-adjuvant setting or for whom anthracyclines were contraindicated. [see Clinical Studies].

The requirement for dose reduction of paclitaxel were higher for patients in the Gemzar/paclitaxel arm (5% versus 2%). The number of paclitaxel doses omitted ( < 1%), the proportion of patients discontinuing treatment for treatment-related adverse reactions (7% versus 5%), and the number of treatment-related deaths (1 patient in each arm) were similar between the two arms.

Table 8: Per-Patient Incidence of Selected Adverse Reactions from Comparative Trial of Gemzar plus Paclitaxel versus Single-Agent Paclitaxel in Breast Cancer^a Occurring at Higher Incidence in Gemzar-Treated Patients [Between Arm Difference of ≥ 5% (All Grades) or ≥ 2% (Grades 3-4)]

The following clinically relevant, Grade 3 or 4 adverse reactions occurred with a higher incidence in the Gemzar plus paclitaxel

Ovarian Cancer

Table 9 presents the incidence of selected adverse reactions, occurring in ≥ 10% of gemcitabine-treated patients and at a higher incidence in the Gemzar plus carboplatin arm, reported in a randomized trial of Gemzar plus carboplatin (n=175) compared to carboplatin alone (n=174) for the second-line treatment of ovarian cancer in women with disease that had relapsed more than 6 months following first-line platinum-based chemotherapy. [see Clinical Studies]. Additional clinically significant adverse reactions, occurring in less than 10% of patients, are provided following Table 9.

The proportion of patients with dose adjustments for carboplatin (1.8% versus 3.8%), doses of carboplatin omitted (0.2% versus 0), and discontinuing treatment for treatment-related adverse reactions (10.9% versus 9.8%), were similar between arms. Dose adjustment for Gemzar occurred in 10.4% of patients and Gemzar dose was omitted in 13.7% of patients in the Gemzar /carboplatin arm.

Table 9: Per-Patient Incidence of Adverse Reactions in Randomized Trial of Gemzar plus Carboplatin versus Carboplatin in Ovarian Cancer Occurring at Higher Incidence in Gemzar-Treated Patients [Between Arm Difference of ≥ 5% (All Grades) or ≥ 2% (Grades 3-4)]

Hematopoietic growth factors were administered more frequently in the Gemzar-containing arm: granulocyte growth factors (23.6% and 10.1%) and erythropoietic agents (7.3% and 3.9%).

The following clinically relevant, Grade 3 and 4 adverse reactions occurred more frequently in the Gemzar plus carboplatin arm: dyspnea (3.4% versus 2.9%), febrile neutropenia (1.1% versus 0), hemorrhagic event (2.3% versus 1.1 %), motor neuropathy (1.1% versus 0.6%), and rash/desquamation (0.6% versus 0).

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Gemzar. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular — Congestive heart failure, myocardial infarction, Arrhythmias, supraventricular arrhythmias.

Vascular Disorders — Peripheral vasculitis, gangrene, and capillary leak syndrome [see WARNINGS AND PRECAUTIONS]

Skin — Cellulitis, severe skin reactions, including desquamation and bullous skin eruptions

Hepatic — Hepatic failure, hepatic veno-occlusive disease

Pulmonary — Interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS)

Read the Gemzar (gemcitabine hcl) Side Effects Center for a complete guide to possible side effects »

No drug interaction studies have been conducted.

Last reviewed on RxList: 6/13/2013
This monograph has been modified to include the generic and brand name in many instances.