Gemcitabine for injection 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 therapy. Gemcitabine for injection in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemother...
Recommended Dose and Schedule The recommended dosage of gemcitabine for injection is 1000 mg/m 2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with carboplatin AUC 4 administered intravenously on Day 1 after gemcitabine for injection administration. Refer to carboplatin prescribing information for additional information. Dosage Modifications Recommended gemcitabine for injection...
Gemcitabine for injection, USP is a white to off-white lyophilized powder available in sterile single-dose vials individually packaged in a carton containing 200 mg or 1 g gemcitabine: 200 mg vial: NDC 55111-686-07 1 g vial: NDC 55111-687-25 Gemcitabine for injection, USP is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room...
www.fda.gov/medwatch
www.osha.gov/SLTC/hazardousdrugs/index.htmlGemcitabine for injection 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 therapy.
Gemcitabine for injection in combination with paclitaxel 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 contraindicated.
Gemcitabine for injection 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).
Gemcitabine for injection is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemcitabine for injection is indicated for patients previously treated with fluorouracil.
Recommended Dose and Schedule
The recommended dosage of gemcitabine for injection is 1000 mg/m2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with carboplatin AUC 4 administered intravenously on Day 1 after gemcitabine for injection administration. Refer to carboplatin prescribing information for additional information.
Dosage Modifications
Recommended gemcitabine for injection dosage modifications for myelosuppression are described in Tables 1 and 2 [see Warnings and Precautions (5.2)]. Refer to the recommended dosage modifications for non-hematologic adverse reactions [see Dosage and Administration (2.5)].
| Treatment Day | Absolute Neutrophil Count (x 106/L) | Platelet Count (x 106/L) | Dosage Modification | |
| Day 1 | Greater than or equal to 1500 | And | Greater than or equal to 100,000 | None |
| Less than 1500 | Or | Less than 100,000 | Delay Treatment Cycle | |
| Day 8 | Greater than or equal to 1500 | And | Greater than or equal to 100,000 | None |
| 1000 to 1499 | Or | 75,000 to 99,999 | 50% of full dose | |
| Less than 1000 | Or | Less than 75,000 | Hold |
| Occurrence | Myelosuppression During Treatment Cycle | Dosage Modification |
| Initial Occurrence |
| Permanently reduce gemcitabine for injection to 800 mg/m2 on Days 1 and 8 |
| Subsequent Occurrence | If any of the above toxicities occur after the initial dose reduction: | Permanently reduce gemcitabine for injection to 800 mg/m2 on Day 1 only |
Recommended Dose and Schedule
The recommended dosage of gemcitabine for injection is 1250 mg/m2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion on Day 1 before gemcitabine for injection administration. Refer to paclitaxel prescribing information for additional information.
Dosage Modifications
Recommended gemcitabine for injection dosage modifications for myelosuppression are described in Table 3 [see Warnings and Precautions (5.2)]. Refer to the recommended dosage modifications for non-hematologic adverse reactions [see Dosage and Administration (2.5)].
| Treatment Day | Absolute Neutrophil Count (x 106/L) | Platelet Count (x 106/L) | Dosage Modification | |
| Day 1 | Greater than or equal to 1500 | And | Greater than or equal to 100,000 | None |
| Less than 1500 | Or | Less than 100,000 | Hold | |
| Day 8 | Greater than or equal to 1200 | And | Greater than 75,000 | None |
| 1000 to 1199 | Or | 50,000 to 75,000 | 75% of full dose | |
| 700 to 999 | And | Greater than or equal to 50,000 | 50% of full dose | |
| Less than 700 | Or | Less than 50,000 | Hold |
Recommended Dose and Schedule
28-day schedule
The recommended dosage of gemcitabine for injection is 1000 mg/m2 intravenously over 30 minutes on Days 1, 8, and 15 of each 28-day cycle in combination with cisplatin 100 mg/m2 administered intravenously on Day 1 after gemcitabine for injection administration.
21-day schedule
The recommended dosage of gemcitabine for injection is 1250 mg/m2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with cisplatin 100 mg/m2 administered intravenously on Day 1 after gemcitabine for injection administration.
Refer to cisplatin prescribing information for additional information.
Recommended Dose and Schedule
The recommended dosage of gemcitabine for injection is 1000 mg/m2 intravenously over 30 minutes. The recommended treatment schedule is as follows:
Dosage Modifications
Recommended dosage modifications for gemcitabine for injection for myelosuppression are described in Table 4 [see Warnings and Precautions (5.2)]. Refer to the recommended dosage modifications for non-hematologic adverse reactions [see Dosage and Administration (2.5)].
| Absolute Neutrophil Count (x 106/L) | Platelet Count (x 106/L) | Dosage Modification | |
| Greater than or equal to 1000 | And | Greater than or equal to 100,000 | None |
| 500 to 999 | Or | 50,000 to 99,999 | 75% of full dose |
| Less than 500 | Or | Less than 50,000 | Hold |
Permanently discontinue gemcitabine for injection for any of the following:
Withhold gemcitabine for injection or reduce dose by 50% for other Grade 3 or 4 non-hematological adverse reactions until resolved. No dose modifications are recommended for alopecia, nausea, or vomiting.
Gemcitabine for Injection USP, 200 mg is a white to off-white, lyophilized powder available in a sterile single-dose vial containing 200 mg gemcitabine.
Gemcitabine for Injection USP, 1 g is a white to off-white, lyophilized powder available in a sterile single-dose vial containing 1 g gemcitabine.
Gemcitabine for injection is contraindicated in patients with a known hypersensitivity to gemcitabine. Reactions include anaphylaxis [see Adverse Reactions (6.1)].
In clinical trials evaluating the maximum tolerated dose of gemcitabine for injection, 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 for injection is influenced by the length of the infusion [see Clinical Pharmacology (12.3)]. Refer to the recommended gemcitabine for injection dosage [see Dosage and Administration (2.1, 2.2, 2.3, 2.4)].
Myelosuppression manifested by neutropenia, thrombocytopenia, and anemia occurs with gemcitabine for injection as a single agent and the risks are increased when gemcitabine for injection is combined with other cytotoxic drugs. In clinical trials, Grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 25%, 8%, and 5%, respectively of the 979 patients who received single agent gemcitabine for injection. The frequencies of Grade 3-4 neutropenia, anemia, and thrombocytopenia varied from 48% to 71%, 8% to 28%, and 5% to 55%, respectively, in patients receiving gemcitabine for injection in combination with another drug [see Adverse Reactions (6.1)].
Prior to each dose of gemcitabine for injection, obtain a complete blood count (CBC) with a differential and a platelet count. Modify the dosage as recommended [see Dosage and Administration (2.1, 2.2, 2.3, 2.4)].
SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia andsystemic symptoms (DRESS), and acute generalizedexanthematous pustulosis (AGEP), which can be life-threatening orfatal, have been reported in association with gemcitabine treatment [see Adverse Reactions (6.2)]. Monitor patients for signs and symptoms of severe cutaneous adverse reactions. Permanently discontinue gemcitabine in patients who develop SCARs.
Pulmonary toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and adult respiratory distress syndrome (ARDS), has been reported. In some cases, these pulmonary events can lead to fatal respiratory failure despite the discontinuation of therapy. The onset of pulmonary symptoms may occur up to 2 weeks after the last dose of gemcitabine for injection [see Adverse Reactions (6.1, 6.2)].
Permanently discontinue gemcitabine for injection in patients who develop unexplained dyspnea, with or without bronchospasm, or evidence of severe pulmonary toxicity.
Hemolytic uremic syndrome (HUS), including fatalities from renal failure or the requirement for dialysis, can occur with gemcitabine for injection. In clinical trials, HUS occurred in 0.25% of 2429 patients. Most fatal cases of renal failure were due to HUS [see Adverse Reactions (6.1)]. Serious cases of thrombotic microangiopathy other than HUS have been reported with gemcitabine for injection [see Adverse Reactions (6.2)].
Assess renal function prior to initiation of gemcitabine for injection and periodically during treatment. Consider the diagnosis of HUS in patients who develop anemia with evidence of microangiopathic hemolysis; increased bilirubin or LDH; reticulocytosis; severe thrombocytopenia; or renal failure (increased serum creatinine or BUN). Permanently discontinue gemcitabine for injection in patients with HUS or severe renal impairment. Renal failure may not be reversible even with the discontinuation of therapy.
Drug-induced liver injury, including liver failure and death, has been reported in patients receiving gemcitabine for injection alone or with other potentially hepatotoxic drugs [see Adverse Reactions (6.1, 6.2)]. Administration of gemcitabine for injection in patients with concurrent liver metastases or a pre-existing medical history of hepatitis, alcoholism, or liver cirrhosis can lead to exacerbation of the underlying hepatic insufficiency. Assess hepatic function prior to initiation of gemcitabine for injection and periodically during treatment. Permanently discontinue gemcitabine for injection in patients who develop severe hepatic toxicity.
Based on animal data and its mechanism of action, gemcitabine for injection can cause fetal harm when administered to a pregnant woman. Gemcitabine was teratogenic, embryotoxic, and fetotoxic in mice and rabbits.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 6 months after the final dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 3 months following the final dose [see Use in Specific Populations (8.1, 8.3)].
Gemcitabine for injection is not recommended for use in combination with radiation therapy.
Concurrent (given together or ≤7 days apart)
Life-threatening mucositis, especially esophagitis and pneumonitis occurred in a trial in which gemcitabine for injection was administered at a dose of 1000 mg/m2 to patients with non-small cell lung cancer for up to 6 consecutive weeks concurrently with thoracic radiation.
Non-concurrent (given >7 days apart)
Excessive toxicity has not been observed when gemcitabine for injection is administered more than 7 days before or after radiation. Radiation recall has been reported in patients who received gemcitabine for injection after prior radiation.
Capillary leak syndrome (CLS) with severe consequences has been reported in patients receiving gemcitabine for injection as a single agent or in combination with other chemotherapeutic agents [see Adverse Reactions (6.2)]. Permanently discontinue gemcitabine for injection if CLS develops during therapy.
Posterior reversible encephalopathy syndrome (PRES) has been reported in patients receiving gemcitabine for injection as a single agent or in combination with other chemotherapeutic agents [see Adverse Reactions (6.2)]. PRES can present with headache, seizure, lethargy, hypertension, confusion, blindness, and other visual and neurologic disturbances. Confirm the diagnosis of PRES with magnetic resonance imaging (MRI). Permanently discontinue gemcitabine for injection if PRES develops during therapy.
The following clinically significant adverse reactions are described elsewhere in the labeling:
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 for injection as a single agent administered at doses between 800 mg/m2 to 1250 mg/m2 intravenously over 30 minutes once weekly in 979 patients with various malignancies. The most common (≥20%) adverse reactions of single agent gemcitabine for injection 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 for injection due to adverse reactions. Adverse reactions resulting in discontinuation of gemcitabine for injection in 2% of 979 patients were cardiovascular adverse reactions (myocardial infarction, cerebrovascular accident, arrhythmia, and hypertension) and adverse reactions resulting in discontinuation of gemcitabine for injection in <1% of 979 patients were anemia, thrombocytopenia, hepatic dysfunction, renal dysfunction, nausea/vomiting, fever, rash, dyspnea, hemorrhage, infection, stomatitis, somnolence, flu-like syndrome, and edema.
Tables 5 and 6 present the incidence of selected adverse reactions and laboratory abnormalities reported in patients with various malignancies receiving single agent gemcitabine for injection across 5 clinical trials. Additional clinically significant adverse reactions are provided following Table 6.
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| Adverse Reactionsb | Gemcitabine For Injectionc | ||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Nausea and Vomiting | 69 | 13 | 1 |
| Fever | 41 | 2 | 0 |
| Rash | 30 | <1 | 0 |
| Dyspnea | 23 | 3 | <1 |
| Diarrhea | 19 | 1 | 0 |
| Hemorrhage | 17 | <1 | <1 |
| Infection | 16 | 1 | <1 |
| Alopecia | 15 | <1 | 0 |
| Stomatitis | 11 | <1 | 0 |
| Somnolence | 11 | <1 | <1 |
| Paresthesias | 10 | <1 | 0 |
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| Laboratory Abnormalityb | Gemcitabine For Injectionc | ||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Hematologic | |||
| Anemia | 68 | 7 | 1 |
| Neutropenia | 63 | 19 | 6 |
| Thrombocytopenia | 24 | 4 | 1 |
| Hepatic | |||
| Increased ALT | 68 | 8 | 2 |
| Increased AST | 67 | 6 | 2 |
| Increased Alkaline Phosphatase | 55 | 7 | 2 |
| Hyperbilirubinemia | 13 | 2 | <1 |
| Renal | |||
| Proteinuria | 45 | <1 | 0 |
| Hematuria | 35 | <1 | 0 |
| Increased BUN | 16 | 0 | 0 |
| Increased Creatinine | 8 | <1 | 0 |
Additional adverse reactions include the following:
Ovarian Cancer
Tables 7 and 8 present the incidence of selected adverse reactions and laboratory abnormalities, occurring in ≥10% of gemcitabine for injection-treated patients and at a higher incidence in the gemcitabine for injection with carboplatin arm, reported in a randomized trial (Study 1) of gemcitabine for injection with 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 (14.1)]. Additional clinically significant adverse reactions, occurring in <10% of patients, are provided following Table 8.
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 adverse reactions (11% versus 10%), were similar between arms. Dose adjustment for gemcitabine for injection occurred in 10% of patients and gemcitabine for injection dose was omitted in 14% of patients in the gemcitabine for injection/carboplatin arm.
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| Adverse Reactionsb | Gemcitabine for Injection/Carboplatin (N=175) | Carboplatin (N=174) | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Nausea | 69 | 6 | 0 | 61 | 3 | 0 |
| Alopecia | 49 | 0 | 0 | 17 | 0 | 0 |
| Vomiting | 46 | 6 | 0 | 36 | 2 | <1 |
| Constipation | 42 | 6 | 1 | 37 | 3 | 0 |
| Fatigue | 40 | 3 | <1 | 32 | 5 | 0 |
| Diarrhea | 25 | 3 | 0 | 14 | <1 | 0 |
| Stomatitis/Pharyngitis | 22 | <1 | 0 | 13 | 0 | 0 |
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| Laboratory Abnormalityb | Gemcitabine for Injection/Carboplatin (N=175) | Carboplatin (N=174) | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Hematologic | ||||||
| Neutropenia | 90 | 42 | 29 | 58 | 11 | 1 |
| Anemia | 86 | 22 | 6 | 75 | 9 | 2 |
| Thrombocytopenia | 78 | 30 | 5 | 57 | 10 | 1 |
| RBC Transfusionsc | 38 | - | - | 15 | - | - |
| Platelet Transfusionsc | 9 | - | - | 3 | - | - |
Hematopoietic growth factors were administered more frequently in the gemcitabine for injection-containing arm: leukocyte growth factor (24% and 10%) and erythropoiesis-stimulating agent (7% and 3.9%).
The following clinically relevant Grade 3 and 4 adverse reactions occurred more frequently in the gemcitabine for injection with 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).
Breast Cancer
Tables 9 and 10 present the incidence of selected adverse reactions and laboratory abnormalities, occurring in ≥10% of gemcitabine for injection-treated patients and at a higher incidence in the gemcitabine for injection with paclitaxel arm, reported in a randomized trial (Study 2) of gemcitabine for injection with 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 (14.2)]. Additional clinically significant adverse reactions, occurring in <10% of patients, are provided following Table 10.
The requirement for dose reduction of paclitaxel were higher for patients in the gemcitabine for injection/paclitaxel arm (5% versus 2%). The number of paclitaxel doses omitted (<1%), the proportion of patients discontinuing treatment for adverse reactions (7% versus 5%) and the number of treatment-related deaths (1 patient in each arm) were similar between the two arms.
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| Adverse Reactionsb | Gemcitabine for Injection/Paclitaxel (N=262) | Paclitaxel (N=259) | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Alopecia | 90 | 14 | 4 | 92 | 19 | 3 |
| Neuropathy-Sensory | 64 | 5 | <1 | 58 | 3 | 0 |
| Nausea | 50 | 1 | 0 | 31 | 2 | 0 |
| Fatigue | 40 | 6 | <1 | 28 | 1 | <1 |
| Vomiting | 29 | 2 | 0 | 15 | 2 | 0 |
| Diarrhea | 20 | 3 | 0 | 13 | 2 | 0 |
| Anorexia | 17 | 0 | 0 | 12 | <1 | 0 |
| Neuropathy-Motor | 15 | 2 | <1 | 10 | <1 | 0 |
| Stomatitis/Pharyngitis | 13 | 1 | <1 | 8 | <1 | 0 |
| Fever | 13 | <1 | 0 | 3 | 0 | 0 |
| Rash/Desquamation | 11 | <1 | <1 | 5 | 0 | 0 |
| Febrile Neutropenia | 6 | 5 | <1 | 2 | 1 | 0 |
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| Laboratory Abnormalityb | Gemcitabine for Injection/Paclitaxel (N=262) | Paclitaxel (N=259) | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Hematologic | ||||||
| Anemia | 69 | 6 | 1 | 51 | 3 | <1 |
| Neutropenia | 69 | 31 | 17 | 31 | 4 | 7 |
| Thrombocytopenia | 26 | 5 | <1 | 7 | <1 | <1 |
| Hepatobiliary | ||||||
| Increased ALT | 18 | 5 | <1 | 6 | <1 | 0 |
| Increased AST | 16 | 2 | 0 | 5 | <1 | 0 |
Clinically relevant Grade 3 or 4 dyspnea occurred with a higher incidence in the gemcitabine for injection with paclitaxel arm compared with the paclitaxel arm (1.9% versus 0).
Non-Small Cell Lung Cancer
Tables 11 and 12 present the incidence of selected adverse reactions and laboratory abnormalities occurring in ≥10% of gemcitabine for injection-treated patients and at a higher incidence in the gemcitabine for injection with cisplatin arm, reported in a randomized trial (Study 3) of gemcitabine for injection with cisplatin (n=260) administered in 28-day cycles as compared to cisplatin alone (n=262) in patients receiving first-line treatment for locally advanced or metastatic NSCLC [see Clinical Studies (14.3)].
Patients randomized to gemcitabine for injection with cisplatin received a median of 4 cycles of treatment and those randomized to cisplatin alone 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 gemcitabine for injection with cisplatin compared to those receiving cisplatin alone. The incidence of febrile neutropenia (3% versus <1%), sepsis (4% versus 1%), Grade 3 cardiac dysrhythmias (3% versus <1%) were all higher in the gemcitabine for injection with 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.
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| Adverse Reactionsb | Gemcitabine For Injection/Cisplatinc | Cisplatind | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Nausea | 93 | 25 | 2 | 87 | 20 | <1 |
| Vomiting | 78 | 11 | 12 | 71 | 10 | 9 |
| Alopecia | 53 | 1 | 0 | 33 | 0 | 0 |
| Neuro Motor | 35 | 12 | 0 | 15 | 3 | 0 |
| Diarrhea | 24 | 2 | 2 | 13 | 0 | 0 |
| Neuro Sensory | 23 | 1 | 0 | 18 | 1 | 0 |
| Infection | 18 | 3 | 2 | 12 | 1 | 0 |
| Fever | 16 | 0 | 0 | 5 | 0 | 0 |
| Neuro Cortical | 16 | 3 | 1 | 9 | 1 | 0 |
| Neuro Mood | 16 | 1 | 0 | 10 | 1 | 0 |
| Local | 15 | 0 | 0 | 6 | 0 | 0 |
| Neuro Headache | 14 | 0 | 0 | 7 | 0 | 0 |
| Stomatitis | 14 | 1 | 0 | 5 | 0 | 0 |
| Hemorrhage | 14 | 1 | 0 | 4 | 0 | 0 |
| Hypotension | 12 | 1 | 0 | 7 | 1 | 0 |
| Rash | 11 | 0 | 0 | 3 | 0 | 0 |
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| Laboratory Abnormalityb | Gemcitabine For Injection/Cisplatinc
| Cisplatind
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| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Hematologic | ||||||
| Anemia | 89 | 22 | 3 | 67 | 6 | 1 |
| Thrombocytopenia | 85 | 25 | 25 | 13 | 3 | 1 |
| Neutropenia | 79 | 22 | 35 | 20 | 3 | 1 |
| Lymphopenia | 75 | 25 | 18 | 51 | 12 | 5 |
| RBC Transfusionse | 39 | - | - | 13 | - | - |
| Platelet Transfusionse | 21 | - | - | <1 | - | - |
| Hepatic | ||||||
| Increased Transaminases | 22 | 2 | 1 | 10 | 1 | 0 |
| Increased Alkaline Phosphatase | 19 | 1 | 0 | 13 | 0 | 0 |
| Renal | ||||||
| Increased Creatinine | 38 | 4 | <1 | 31 | 2 | <1 |
| Proteinuria | 23 | 0 | 0 | 18 | 0 | 0 |
| Hematuria | 15 | 0 | 0 | 13 | 0 | 0 |
| Other Laboratory | ||||||
| Hyperglycemia | 30 | 4 | 0 | 23 | 3 | 0 |
| Hypomagnesemia | 30 | 4 | 3 | 17 | 2 | 0 |
| Hypocalcemia | 18 | 2 | 0 | 7 | 0 | <1 |
Tables 13 and 14 present the incidence of selected adverse reactions and laboratory abnormalities occurring in ≥10% of gemcitabine for injection-treated patients and at a higher incidence in the gemcitabine for injection with cisplatin arm, reported in a randomized trial (Study 4) of gemcitabine for injection with cisplatin (n=69) administered in 21-day cycles as compared to etoposide with cisplatin (n=66) in patients receiving first-line treatment for locally advanced or metastatic NSCLC [see Clinical Studies (14.3)]. Additional clinically significant adverse reactions are provided following Table 14.
Patients in the gemcitabine for injection/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 adverse reactions was 22% in the GC arm and 27% in the EC arm. The proportion of patients who discontinued treatment for adverse reactions was higher in the GC arm (14% versus 8%). The proportion of patients who were 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 GC arm.
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| Adverse Reactionsb | Gemcitabine For Injection/Cisplatinc | Etoposide/Cisplatind | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Nausea and Vomiting | 96 | 35 | 4 | 86 | 19 | 7 |
| Alopecia | 77 | 13 | 0 | 92 | 51 | 0 |
| Paresthesias | 38 | 0 | 0 | 16 | 2 | 0 |
| Infection | 28 | 3 | 1 | 21 | 8 | 0 |
| Stomatitis | 20 | 4 | 0 | 18 | 2 | 0 |
| Diarrhea | 14 | 1 | 1 | 13 | 0 | 2 |
| Edemae | 12 | - | - | 2 | - | - |
| Rash | 10 | 0 | 0 | 3 | 0 | 0 |
| Hemorrhage | 9 | 0 | 3 | 3 | 0 | 3 |
| Fever | 6 | 0 | 0 | 3 | 0 | 0 |
| Somnolence | 3 | 0 | 0 | 3 | 2 | 0 |
| Flu-like Syndromee | 3 | - | - | 0 | - | - |
| Dyspnea | 1 | 0 | 1 | 3 | 0 | 0 |
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| Laboratory Abnormalityb | Gemcitabine For Injection/Cisplatinc | Etoposide/Cisplatind | ||||
| All Grades (%) | Grade 3 (%) | Grade 4 (%) | All Grades (%) | Grade 3 (%) | Grade 4 (%) | |
| Hematologic | ||||||
| Anemia | 88 | 22 | 0 | 77 | 13 | 2 |
| Neutropenia | 88 | 36 | 28 | 87 | 20 | 56 |
| Thrombocytopenia | 81 | 39 | 16 | 45 | 8 | 5 |
| RBC Transfusionsc | 29 | - | - | 21 | - | - |
| Platelet Transfusionse | 3 | - | - | 8 | - | - |
| Hepatic | ||||||
| Increased Alkaline Phosphatase | 16 | 0 | 0 | 11 | 0 | 0 |
| Increased ALT | 6 | 0 | 0 | 12 | 0 | 0 |
| Increased AST | 3 | 0 | 0 | 11 | 0 | 0 |
| Renal | ||||||
| Hematuria | 22 | 0 | 0 | 10 | 0 | 0 |
| Proteinuria | 12 | 0 | 0 | 5 | 0 | 0 |
| Increased BUN | 6 | 0 | 0 | 4 | 0 | 0 |
| Increased Creatinine | 2 | 0 | 0 | 2 | 0 | 0 |
The following adverse reactions have been identified during post approval use of gemcitabine for injection. 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.
Risk Summary
Based on animal data and its mechanism of action, gemcitabine for injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of gemcitabine for injection in pregnant women. In animal reproduction studies, gemcitabine was teratogenic, embryotoxic, and fetotoxic in mice and rabbits (see Data). Advise pregnant women of the potential risk to a fetus [see Use in Special Populations (8.3)].
In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20% respectively.
Data
Animal Data
Gemcitabine is embryotoxic in mice. Daily dosing of gemcitabine to pregnant mice increased the incidence of fetal malformation (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day [approximately 0.005 times the 1000 mg/m2 clinical dose based on body surface area (BSA)]. Gemcitabine was embryotoxic and fetotoxic in rabbits. Daily dosing of gemcitabine to pregnant rabbits resulted in fetotoxicity (decreased fetal viability, reduced litter sizes, and developmental delays) and increased the incidence of fetal malformations (fused pulmonary artery, absence of gall bladder) at doses of 0.1 mg/kg/day (approximately 0.002 times the 1000 mg/m2 clinical dose based on BSA).
Risk Summary
There is no information regarding the presence of gemcitabine for injection or its metabolites in human milk, or their effects on the breastfed infant or on milk production. Due to the potential for serious adverse reactions in breastfed infants from gemcitabine for injection, advise women not to breastfeed during treatment with gemcitabine for injection and for at least one week following the last dose.
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating gemcitabine for injection [see Use in Specific Populations (8.1)].
Contraception
Gemcitabine for injection can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Females
Because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 6 months after the final dose of gemcitabine for injection.
Males
Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 3 months after the final dose [see Nonclinical Toxicology (13.1)].
Infertility
Males
Based on animal studies, gemcitabine for injection may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1)]. It is not known whether these effects on fertility are reversible.
The safety and effectiveness of gemcitabine for injection have not been established in pediatric patients.
The safety and pharmacokinetics of gemcitabine were evaluated in a trial in pediatric patients with refractory leukemia. The maximum tolerated dose was 10 mg/m2/min for 360 minutes weekly for three weeks followed by a one-week rest period.
The safety and activity of gemcitabine for injection were evaluated in a trial of pediatric patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) at a dose of 10 mg/m2/min administered over 360 minutes weekly for three weeks followed by a one-week rest period. Patients with M1 or M2 bone marrow on Day 28 who did not experience unacceptable toxicity were eligible to receive a maximum of one additional four-week course. Toxicities observed included myelosuppression, febrile neutropenia, increased serum transaminases, nausea, and rash/desquamation. No meaningful clinical activity was observed in this trial.
In clinical studies which enrolled 979 patients with various malignancies who received single agent gemcitabine for injection, no overall differences in safety were observed between patients aged 65 and older and younger patients, with the exception of a higher rate of Grade 3-4 thrombocytopenia in older patients as compared to younger patients.
In a randomized trial in women with ovarian cancer (Study 1), 175 women received gemcitabine for injection with carboplatin, of which 29% were age 65 years or older. Similar effectiveness was observed between older and younger women. There was significantly higher Grade 3-4 neutropenia in women 65 years of age or older [see Dosage and Administration (2.1)].
Gemcitabine for injection clearance is affected by age; however, there are no recommended dose adjustments based on patients' age [see Clinical Pharmacology (12.3)].
Gemcitabine for injection clearance is decreased in females [see Clinical Pharmacology (12.3)]. In single agent studies of gemcitabine for injection, women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3-4 neutropenia and thrombocytopenia [see Dosage and Administration (2.1, 2.2. 2.3, 2.4)].
There is no known antidote for overdoses of gemcitabine. Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5700 mg/m2 was administered by intravenous infusion over 30 minutes every 2 weeks to several patients in a dose-escalation study. In the event of suspected overdose, monitor with appropriate blood counts and provide supportive therapy, as necessary.
Gemcitabine is a nucleoside metabolic inhibitor. Gemcitabine hydrochloride is 2′-deoxy-2′,2′-difluorocytidine monohydrochloride (β-isomer) with the following structural formula:
The empirical formula for gemcitabine hydrochloride is C9H11F2N3O4 • HCl. It has a molecular weight of 299.66 g/mol.
Gemcitabine HCl, USP is a white to off-white solid. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.
Gemcitabine for injection, USP is a white to off-white lyophilized powder and available as 200 mg and 1 g sterile single-dose vials for intravenous use only. Each 200 mg vial contains 200 mg gemcitabine hydrochloride (expressed as free base), 200 mg mannitol and 20.73 mg of sodium acetate trihydrate (equivalent to 12.5 mg of sodium acetate anhydrous). Each 1 g vial contains 1 g gemcitabine hydrochloride (expressed as free base), 1 g mannitol, and 103.5 mg of sodium acetate trihydrate (equivalent to 62.5 mg of sodium acetate anhydrous). Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.
Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary. Gemcitabine is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabine diphosphate inhibits ribonucleotide reductase, an enzyme responsible for catalyzing the reactions that generate deoxynucleoside triphosphates for DNA synthesis, resulting in reductions in deoxynucleotide concentrations, including dCTP. Gemcitabine triphosphate competes with dCTP for incorporation into DNA. The reduction in the intracellular concentration of dCTP by the action of the diphosphate enhances the incorporation of gemcitabine triphosphate into DNA (self-potentiation). After the gemcitabine nucleotide is incorporated into DNA, only one additional nucleotide is added to the growing DNA strands, which eventually results in the initiation of apoptotic cell death.
The pharmacokinetics of gemcitabine were examined in 353 patients with various solid tumors. Pharmacokinetic parameters were derived using data from patients treated for varying durations of therapy given weekly with periodic rest weeks and using both short infusions (<70 minutes) and long infusions (70 to 285 minutes). The total gemcitabine for injection dose varied from 500 mg/m2 to 3600 mg/m2.
Distribution
The volume of distribution was increased with infusion length. Volume of distribution of gemcitabine was 50 L/m2 following infusions lasting <70 minutes. For long infusions, the volume of distribution rose to 370 L/m2.
Gemcitabine pharmacokinetics are linear and are described by a 2-compartment model. Population pharmacokinetic analyses of combined single and multiple dose studies showed that the volume of distribution of gemcitabine was significantly influenced by duration of infusion and sex. Gemcitabine plasma protein binding is negligible.
Elimination
Metabolism
The active metabolite, gemcitabine triphosphate, can be extracted from peripheral blood mononuclear cells. The half-life of the terminal phase for gemcitabine triphosphate from mononuclear cells ranges from 1.7 to 19.4 hours.
Excretion
Gemcitabine disposition was studied in 5 patients who received a single 1000 mg/m2 of radiolabeled drug as a 30-minute infusion. Within one week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2′-deoxy-2′,2′-difluorouridine (dFdU) accounted for 99% of the excreted dose. The metabolite dFdU is also found in plasma.
Specific Populations
Geriatric Patients
Clearance of gemcitabine was affected by age. The lower clearance in geriatric patients results in higher concentrations of gemcitabine for any given dose. Differences in either clearance or volume of distribution based on patient characteristics or the duration of infusion result in changes in half-life and plasma concentrations. Table 15 shows plasma clearance and half-life of gemcitabine following short infusions for typical patients by age and sex.
| ||||
| Age | Clearance Men (L/hr/m2) | Clearance Women (L/hr/m2) | Half-Lifea Men (min) | Half-Lifea Women (min) |
| 29 | 92.2 | 69.4 | 42 | 49 |
| 45 | 75.7 | 57.0 | 48 | 57 |
| 65 | 55.1 | 41.5 | 61 | 73 |
| 79 | 40.7 | 30.7 | 79 | 94 |
Gemcitabine half-life for short infusions ranged from 42 to 94 minutes and for long infusions varied from 245 to 638 minutes, depending on age and sex, reflecting a greatly increased volume of distribution with longer infusions.
Male and Female Patients
Females have lower clearance and longer half-lives than male patients as described in Table 15.
Patients with Renal Impairment
No clinical studies have been conducted with gemcitabine in patients with decreased renal function.
Patients with Hepatic Impairment
No clinical studies have been conducted with gemcitabine in patients with decreased hepatic function.
Drug Interaction Studies
When gemcitabine for injection (1250 mg/m2 on Days 1 and 8) and cisplatin (75 mg/m2 on Day 1) were administered in patients with NSCLC, the clearance of gemcitabine on Day 1 was 128 L/hr/m2 and on Day 8 was 107 L/hr/m2. Data from patients with NSCLC demonstrate that gemcitabine for injection and carboplatin given in combination does not alter the pharmacokinetics of gemcitabine or carboplatin compared to administration of either single agent; however, due to wide confidence intervals and small sample size, interpatient variability may be observed.
Data from metastatic breast cancer patients shows that gemcitabine for injection has little or no effect on the pharmacokinetics (clearance and half-life) of paclitaxel and paclitaxel has little or no effect on the pharmacokinetics of gemcitabine.
Long-term animal studies to evaluate the carcinogenic potential of gemcitabine for injection have not been conducted. Gemcitabine was mutagenic in an in vitro mouse lymphoma (L5178Y) assay and was clastogenic in an in vivo mouse micronucleus assay. Gemcitabine intraperitoneal doses of 0.5 mg/kg/day [about 1/700 the 1000 mg/m2 clinical dose based on body surface area (BSA)] in male mice resulted in moderate to severe hypospermatogenesis, decreased fertility, and decreased implantations. In female mice, fertility was not affected but maternal toxicities were observed at 1.5 mg/kg/day administered intravenously (about 1/200 the 1000 mg/m2 clinical dose based on BSA) and fetotoxicity or embryolethality was observed at 0.25 mg/kg/day administered intravenously (about 1/1300 the 1000 mg/m2 clinical dose based on BSA).
The efficacy of gemcitabine for injection was evaluated in a randomized trial (Study 1) conducted in women with advanced ovarian cancer that had relapsed at least 6 months after first-line platinum-based therapy. Patients were randomized to receive either gemcitabine for injection 1000 mg/m2 on Days 1 and 8 of each 21-day cycle with carboplatin AUC 4 on Day 1 after gemcitabine for injection administration (n=178) or carboplatin AUC 5 on Day 1 of each 21-day cycle (n=178). The major efficacy outcome measure was progression free survival (PFS).
A total of 356 patients were enrolled. Demographics and baseline characteristics are shown in Table 16.
Efficacy results are presented in Table 17 and Figure 1. The addition of gemcitabine for injection to carboplatin resulted in statistically significant improvements in PFS and overall response rate. Approximately 75% of patients in each arm received additional chemotherapy for disease progression; 13 of 120 patients in the carboplatin alone arm received gemcitabine for injection for treatment of disease progression. There was no significant difference in overall survival between the treatment arms.
| ||
| ||
| Gemcitabine For Injection/Carboplatin (N=178) | Carboplatin (N=178) | |
| Median age, years | 59 | 58 |
| Range | 36 to 78 | 21 to 81 |
| Baseline ECOG performance status 0-1a | 94% | 95% |
| Disease Status | ||
| Evaluable | 8% | 3% |
| Bidimensionally measurable | 92% | 96% |
| Platinum-free intervalb | ||
| 6-12 months | 40% | 40% |
| >12 months | 59% | 60% |
| First-line therapy | ||
| Platinum-taxane combination | 70% | 71% |
| Platinum-non-taxane combination | 29% | 28% |
| Platinum monotherapy | 1% | 1% |
| ||
| ||
| ||
| ||
| ||
| ||
| Efficacy Parameter | Gemcitabine For Injection/Carboplatin (N=178) | Carboplatin (N=178) |
| Progression-Free Survival | ||
| Median (95% CIa) in months | 8.6 (8.0, 9.7) | 5.8 (5.2, 7.1) |
| Hazard Ratio (95% CI) | 0.72 (0.57, 0.90) | |
| p-valueb | p=0.0038 | |
| Overall Survival | ||
| Median (95% CI) in months | 18.0 (16.2, 20.3) | 17.3 (15.2, 19.3) |
| Hazard Ratio (95% CI) | 0.98 (0.78, 1.24) | |
| p-valueb | p=0.8977 | |
| Overall Response Rate by Investigator Review | 47.2% | 30.9% |
| p-valuec | p=0.0016 | |
| CRd | 14.6% | 6.2% |
| PR with PRNMe | 32.6% | 24.7% |
| Overall Response Ratef by Independent Review | 46.3% | 35.6% |
| p-valuec | p=0.11 | |
| CRd | 9.1% | 4.0% |
| PR with PRNMe | 37.2% | 31.7% |
Figure 1: Kaplan-Meier Curves for Progression Free Survival in Study 1
The efficacy of gemcitabine for injection was evaluated in a multinational, randomized, open-label trial (Study 2) conducted in women receiving initial treatment for metastatic breast cancer and who have received prior adjuvant/neoadjuvant anthracycline chemotherapy unless clinically contraindicated. Patients were randomized to receive either gemcitabine for injection 1250 mg/m2 on Days 1 and 8 of each 21-day cycle with paclitaxel 175 mg/m2 administered on Day 1 before gemcitabine for injection administration (n=267) or paclitaxel 175 mg/m2 on Day 1 of each 21-day cycle (n=262). The major efficacy outcome measure was time to documented disease progression.
A total of 529 patients were enrolled. Demographic and baseline characteristics were similar between treatment arms (Table 18).
Efficacy results are presented in Table 19 and Figure 2. The addition of gemcitabine for injection to paclitaxel resulted in statistically significant improvement in time to documented disease progression and overall response rate compared to paclitaxel alone. There was no significant difference in overall survival.
| ||
| Gemcitabine For Injection/Paclitaxel (N=267) | Paclitaxel (N=262) | |
| Median age (years) | 53 | 52 |
| Range | 26 to 83 | 26 to 75 |
| Metastatic disease | 97% | 97% |
| Baseline KPSa ≥90 | 70% | 74% |
| Number of tumor sites | ||
| 1-2 | 57% | 59% |
| ≥3 | 43% | 41% |
| Visceral disease | 73% | 73% |
| Prior anthracycline | 97% | 96% |
| ||
| ||
| Efficacy Parameter | Gemcitabine For Injection/Paclitaxel (N=267) | Paclitaxel (N=262) |
| Time to Documented Disease Progressiona | ||
| Median (95% CI) in months | 5.2 (4.2, 5.6) | 2.9 (2.6, 3.7) |
| Hazard Ratio (95% CI) | 0.650 (0.524, 0.805) | |
| p-value | p<0.0001 | |
| Overall Survivalb | ||
| Median (95% CI) in months | 18.6 (16.5, 20.7) | 15.8 (14.1, 17.3) |
| Hazard Ratio (95% CI) | 0.86 (0.71, 1.04) | |
| p-value | Not Significant | |
| Overall Response Rate | 40.8% | 22.1% |
| (95% CI) | (34.9, 46.7) | (17.1, 27.2) |
| p-value | p<0.0001 | |
Figure 2: Kaplan-Meier Curves for Time to Documented Disease Progression in Study 2
The efficacy of gemcitabine for injection was evaluated in two randomized, multicenter trials.
Study 3: 28-Day Schedule
A multinational, randomized trial (Study 3) compared gemcitabine for injection with cisplatin to cisplatin alone in the treatment of patients with inoperable Stage IIIA, IIIB, or IV NSCLC who had not received prior chemotherapy. Patients were randomized to receive either gemcitabine for injection 1000 mg/m2 on Days 1, 8, and 15 of each 28-day cycle with cisplatin 100 mg/m2 on Day 1 after gemcitabine for injection administration (N=260) or cisplatin 100 mg/m2 on Day 1 of each 28-day cycle (N=262). The major efficacy outcome measure was overall survival.
A total of 522 patients were enrolled. Demographics and baseline characteristics (Table 20) were similar between arms with the exception of histologic subtype of NSCLC, with 48% of patients on the cisplatin arm and 37% of patients on the gemcitabine for injection with cisplatin arm having adenocarcinoma.
Study 4: 21-Day Schedule
A randomized (1:1), multicenter trial (Study 4) was conducted in patients with Stage IIIB or IV NSCLC. Patients were randomized to receive either gemcitabine for injection 1250 mg/m2 on Days 1 and 8 of each 21-day cycle with cisplatin 100 mg/m2 on Day 1 after gemcitabine for injection administration or etoposide 100 mg/m2 intravenously on Days 1, 2, and 3 with cisplatin 100 mg/m2 on Day 1 of each 21 -day cycle. The major efficacy outcome measure was response rate.
A total of 135 patients were enrolled. Demographics and baseline characteristics are summarized in Table 20.
Efficacy results are presented in Table 21. There was no significant difference in survival between the two treatment arms. The median survival was 8.7 months for the gemcitabine for injection with cisplatin arm versus 7 months for the etoposide with cisplatin arm. Median time to disease progression for the gemcitabine for injection with cisplatin arm was 5 months compared to 4.1 months on the etoposide with cisplatin arm (Log rank p=0.015, two-sided). The objective response rate for the gemcitabine for injection with cisplatin arm was 33% compared to 14% on the etoposide with cisplatin arm (Fisher's Exact p=0.01, two-sided).
| ||||
| ||||
| Trial | 28-day Schedule (Study 3) | 21-day Schedule (Study 4) | ||
| Gemcitabine For Injection/ Cisplatin (N=260) | Cisplatin (N=262) | Gemcitabine For Injection/ Cisplatin (N=69) | Etoposide/ Cisplatin (N=66) | |
| Male | 70% | 71% | 93% | 92% |
| Median age, years | 62 | 63 | 58 | 60 |
| Range | 36 to 88 | 35 to 79 | 33 to 76 | 35 to 75 |
| Stage IIIA | 7% | 7% | N/Aa | N/Aa |
| Stage IIIB | 26% | 23% | 48% | 52% |
| Stage IV | 67% | 70% | 52% | 49% |
| Baseline KPSb 70 to 80 | 41% | 44% | 45% | 52% |
| Baseline KPSb 90 to 100 | 57% | 55% | 55% | 49% |
| ||||
| ||||
| Trial | 28-day Schedule (Study 3) | 21-day Schedule (Study 4) | ||
| Efficacy Parameter | Gemcitabine For Injection/ Cisplatin (N=260) | Cisplatin (N=262) | Gemcitabine For Injection/ Cisplatin (N=69) | Etoposide/ Cisplatin (N=66) |
| Survival | ||||
| Median (95% CIa) in months | 9.0 (8.2, 11.0) | 7.6 (6.6, 8.8) | 8.7 (7.8, 10.1) | 7.0 (6.0, 9.7) |
| p-valuef | p=0.008 | p=0.18 | ||
| Time to Disease Progression | ||||
| Median (95% CIa) in months | 5.2 (4.2, 5.7) | 3.7 (3.0, 4.3) | 5.0 (4.2, 6.4) | 4.1 (2.4, 4.5) |
| p-valueb | p=0.009 | p=0.05 | ||
| Tumor Response | 26% | 10% | 33% | 14% |
| p-valueb | p<0.0001 | p=0.01 | ||
Figure 3: Kaplan-Meier Curves for Overall Survival in Study 3
The efficacy of gemcitabine for injection was evaluated in two trials (Studies 5 and 6), a randomized, single-blind, two-arm, active-controlled trial (Study 5) conducted in patients with locally advanced or metastatic pancreatic cancer who had received no prior chemotherapy and in a single-arm, open-label, multicenter trial (Study 6) conducted in patients with locally advanced or metastatic pancreatic cancer previously treated with fluorouracil or a fluorouracil-containing regimen. In Study 5, patients were randomized to receive either gemcitabine for injection 1000 mg/m2 intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles (n=63) or fluorouracil 600 mg/m2 intravenously over 30 minutes once weekly (n=63). In Study 6, all patients received gemcitabine for injection 1000 mg/m2 intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles.
The major efficacy outcome measure in both trials was “clinical benefit response”. A patient was considered to have had a clinical benefit response if either of the following occurred:
Study 5 enrolled 126 patients. Demographics and baseline characteristics were similar between the arms (Table 22).
The efficacy results are shown in Table 23 and Figure 4. Patients treated with gemcitabine for injection had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to those randomized to receive fluorouracil. No confirmed objective tumor responses were observed in either treatment arm.
| ||
| Gemcitabine For Injection (N=63) | Fluorouracil (N=63) | |
| Male | 54% | 54% |
| Median age, years | 62 | 61 |
| Range | 37 to 79 | 36 to 77 |
| Stage IV disease | 71% | 76% |
| Baseline KPSa ≤70 | 70% | 68% |
| ||
| Efficacy Parameter | Gemcitabine For Injection (N=63) | Fluorouracil (N=63) |
| Clinical Benefit Response | 22.2% | 4.8% |
| p-valuea | p=0.004 | |
| Overall Survival | ||
| Median (95% CI) in months | 5.7 (4.7, 6.9) | 4.2 (3.1, 5.1) |
| p-valuea | p=0.0009 | |
| Time to Disease Progression | ||
| Median (95% CI) in months | 2.1 (1.9, 3.4) | 0.9 (0.9, 1.1) |
| p-valuea | p=0.0013 | |
Figure 4: Kaplan-Meier Curves for Overall Survival in Study 5
www.osha.gov/SLTC/hazardousdrugs/index.html
Gemcitabine for injection, USP is a white to off-white lyophilized powder available in sterile single-dose vials individually packaged in a carton containing 200 mg or 1 g gemcitabine:
Gemcitabine for injection, USP is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].
Myelosuppression
Advise patients of the risks of myelosuppression. Instruct patients to immediately contact their healthcare provider should any signs or symptoms of infection, including fever, or if bleeding or signs of anemia, occur [see Warnings and Precautions (5.2)].
Severe Cutaneous Adverse Reactions (SCARs)
Advise patients of the risks of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Instruct patients to immediately contact their healthcare provider should any signs or symptoms of severe skin rash or skin peeling, blistering and/or mouth sores occur [see Warnings and Precautions (5.3)].
Pulmonary Toxicity
Advise patients of the risks of pulmonary toxicity, including respiratory failure and death. Instruct patients to immediately contact their healthcare provider for development of shortness of breath, wheezing, or cough [see Warnings and Precautions (5.4)].
Hemolytic-Uremic Syndrome and Renal Failure
Advise patients of the risks of hemolytic-uremic syndrome and associated renal failure. Instruct patients to immediately contact their healthcare provider for changes in the color or volume of urine output or for increased bruising or bleeding [see Warnings and Precautions (5.5)].
Hepatic Toxicity
Advise patients of the risks of hepatic toxicity including liver failure and death. Instruct patients to immediately contact their healthcare provider for signs of jaundice or for pain/tenderness in the right upper abdominal quadrant [see Warnings and Precautions (5.6)].
Embryo-Fetal Toxicity
Advise females and males of reproductive potential that gemcitabine for injection can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 6 months after the final dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with gemcitabine for injection and for 3 months after the final dose [see Warnings and Precaution (5.7), Use in Specific Populations (8.1, 8.3)].
Lactation
Advise women not to breastfeed during treatment with gemcitabine for injection and for at least one week after the last dose [see Use in Specific Populations (8.2)].
PACKAGE CARTON – Gemcitabine For Injection 200 mg carton 1ct
NDC 55111-686-07
Gemcitabine For Injection, USP
200 mg/vial
PACKAGE CARTON – Gemcitabine For Injection 1 g carton 1ct
NDC 55111-687-25
Gemcitabine For Injection, USP
1 g/vial
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 1719003 | gemcitabine 1 GM Injection | PSN | 16 |
| 1719000 | gemcitabine 200 MG Injection | PSN | 16 |
| 1719003 | gemcitabine 1000 MG Injection | SCD | 16 |
| 1719000 | gemcitabine 200 MG Injection | SCD | 16 |
| 1719003 | gemcitabine (as gemcitamine HCl) 1 GM Injection | SY | 16 |
| 1719000 | gemcitabine (as gemcitamine HCl) 200 MG Injection | SY | 16 |
| 1719003 | gemcitabine 1 GM Injection | SY | 16 |
| Class | Version | Type | Effective |
|---|---|---|---|
| GEMCITABINE Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20180813 |
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| 6bd95106-a412-1dad-b9cc-4cb74bfb27ce | Product name | 2 | 20230315 |
| a2b7d477-0e35-4772-8a9d-99c71e3e210b | Product name | 2 | 20190614 |
| 4c31c9b8-06d5-4f83-9eb7-cd946af7067a | Product name | 5 | 20190612 |
| a12a1c0c-65f2-45a0-8bf0-7dfc55c750b6 | Product name | 1 | 20180829 |
| d2980057-8cff-4896-979e-b4c394974cfd | Product name | 1 | 20170829 |
| d5e51f11-ad28-caa4-4b49-4143974782ad | Product name | 1 | 20150831 |
| 290f523a-f9db-9774-b5a9-e1f908ac1782 | Product name | 1 | 20150828 |
| 0ca1d589-929b-4b33-bc5b-1d84abdafa6a | Product name | 1 | 20150324 |
| fc363c46-397b-4476-ac0f-70e43e8e4592 | Product name | 1 | 20150324 |
| c6b65c52-69c7-df49-550a-a50c137f6218 | Product name | 1 | 20140508 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 55111-686-07 | gemcitabine | 5 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 5 | 16 | |
| 55111-686-07 | gemcitabine | 1 in 1 CARTON | INJECTION, POWDER, LYOPHILIZED, | 1 | 16 | |
| 55111-687-25 | gemcitabine | 25 mL in 1 VIAL, SINGLE-USE | INJECTION, POWDER, LYOPHILIZED, | 25 | 16 | |
| 55111-687-25 | gemcitabine | 1 in 1 CARTON | INJECTION, POWDER, LYOPHILIZED, | 1 | 16 |
| NDC | Dashboard title | SPL version | Validation | Dashboard ZIP |
|---|---|---|---|---|
| 55111-686 | GEMCITABINE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [DR. REDDY'S LABORATORIES LIMITED ] | 16 | Current NDC, Legacy NDC, 2 package rows | 20240919_eafcebc8-ddef-bb6b-fd0a-9d8b9962cdc4.zip |
| 55111-687 | GEMCITABINE INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [DR. REDDY'S LABORATORIES LIMITED ] | 16 | Current NDC, Legacy NDC, 2 package rows | 20240919_eafcebc8-ddef-bb6b-fd0a-9d8b9962cdc4.zip |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 55111-686-07 | EA - Each | 55111-686 | 58c86605-336f-4916-8005-8d23df926707 | 1 | 2012-07-24 |
| 55111-687-25 | EA - Each | 55111-687 | 7f7bdfd4-2546-4f09-8a3a-b0929e941cd8 | 1 | 2012-07-24 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| gemcitabine hydrochloride | ACTIVE INGREDIENT | U347PV74IL | 10 | |
| gemcitabine | ACTIVE MOIETY | B76N6SBZ8R | 10 | |
| MANNITOL | INACTIVE INGREDIENT | 3OWL53L36A | 10 | |
| SODIUM ACETATE | INACTIVE INGREDIENT | 4550K0SC9B | 10 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 55111-686 | 55111-686-07 |
| 55111-687 | 55111-687-25 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| Gemcitabine hydrochloride | U347PV74IL | ACTIM |
| Mannitol | 3OWL53L36A | IACT |
| Sodium acetate | 4550K0SC9B | IACT |
| Gemcitabine hydrochloride | U347PV74IL | ACTIM |
| Mannitol | 3OWL53L36A | IACT |
| Sodium acetate | 4550K0SC9B | IACT |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| MANNITOL | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 15400 mg | ||
| MANNITOL | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 15400 mg | ||
| SODIUM ACETATE | SODIUM ACETATE | 4550K0SC9B | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 141 mg | ||
| MANNITOL | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 15400 mg | ||
| MANNITOL | MANNITOL | 3OWL53L36A | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 15400 mg | ||
| SODIUM ACETATE | SODIUM ACETATE | 4550K0SC9B | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 141 mg | ||
| SODIUM ACETATE | SODIUM ACETATE | 4550K0SC9B | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 141 mg | ||
| SODIUM ACETATE | SODIUM ACETATE | 4550K0SC9B | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 141 mg |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| A091365-001 | GEMCITABINE HYDROCHLORIDE | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | |
| A091365-002 | GEMCITABINE HYDROCHLORIDE | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 |
| Application-product | TE code |
|---|---|
| A091365-001 | AP |
| A091365-002 | AP |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | caaa826d4ba7… | |
| 2026-02-19 14:30 UTC | 2026-02 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 31067a03dcf5… | |
| 2025-08-23 18:47 UTC | 2025-08 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 6a471c1ec25d… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | fd3edfee7708… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | b8a1b40f171c… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 03ed91905a0d… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 2680178bc6a6… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5bbf6a4d5a75… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | d8e5a09893c0… | |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | d8e5a09893c0… | |
| 2024-10-29 15:01 UTC | 2024-10 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | d06236e962d9… | |
| 2024-10-29 15:01 UTC | 2024-10 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | d06236e962d9… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 79d66fd596c7… | |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 79d66fd596c7… | |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 301d65b070ca… | |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 301d65b070ca… | |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 1e350fbaab3a… | |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 1e350fbaab3a… | |
| 2024-05-31 18:47 UTC | 2024-05 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 8072bd15b7f6… | |
| 2024-05-31 18:47 UTC | 2024-05 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 8072bd15b7f6… | |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5c6f7cd8ea54… | |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5c6f7cd8ea54… | |
| 2022-04-08 23:34 UTC | 2022-04 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5d02ea3f76ae… | |
| 2022-04-08 23:34 UTC | 2022-04 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 5d02ea3f76ae… | |
| 2022-04-04 05:41 UTC | 2022-04 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 4b0b4de00fa7… | |
| 2022-04-04 05:41 UTC | 2022-04 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 4b0b4de00fa7… | |
| 2019-12-13 00:20 UTC | 2019-12 | A091365-001 | GEMCITABINE HYDROCHLORIDE | EQ 200MG BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 74a2ff9319b5… | |
| 2019-12-13 00:20 UTC | 2019-12 | A091365-002 | GEMCITABINE HYDROCHLORIDE | EQ 1GM BASE/VIAL | INJECTABLE / INJECTION | AP | 2011-07-25 | 74a2ff9319b5… |
| Captured | Edition | Application-product | TE code | Order | Source SHA-256 |
|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | A091365-001 | AP | 1 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | A091365-002 | AP | 1 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | A091365-001 | AP | 1 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | A091365-002 | AP | 1 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | A091365-001 | AP | 1 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | A091365-002 | AP | 1 | 011fe1cb6892… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A091365-001 | AP | 1 | 31067a03dcf5… |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | A091365-002 | AP | 1 | 31067a03dcf5… |
| 2025-08-23 18:47 UTC | 2025-08 | A091365-001 | AP | 1 | 6a471c1ec25d… |
| 2025-08-23 18:47 UTC | 2025-08 | A091365-002 | AP | 1 | 6a471c1ec25d… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A091365-001 | AP | 1 | fd3edfee7708… |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | A091365-002 | AP | 1 | fd3edfee7708… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A091365-001 | AP | 1 | b8a1b40f171c… |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | A091365-002 | AP | 1 | b8a1b40f171c… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A091365-001 | AP | 1 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | A091365-002 | AP | 1 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A091365-001 | AP | 1 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | A091365-002 | AP | 1 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A091365-001 | AP | 1 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | A091365-002 | AP | 1 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A091365-001 | AP | 1 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | A091365-002 | AP | 1 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | A091365-001 | AP | 1 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | A091365-002 | AP | 1 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A091365-001 | AP | 1 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | A091365-002 | AP | 1 | 79d66fd596c7… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A091365-001 | AP | 1 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | A091365-002 | AP | 1 | 301d65b070ca… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A091365-001 | AP | 1 | 1e350fbaab3a… |
| 2024-06-18 03:08 UTC · 5 captures of this ZIP | 2024-06 | A091365-002 | AP | 1 | 1e350fbaab3a… |
| 2024-05-31 18:47 UTC | 2024-05 | A091365-001 | AP | 1 | 8072bd15b7f6… |
| 2024-05-31 18:47 UTC | 2024-05 | A091365-002 | AP | 1 | 8072bd15b7f6… |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | A091365-001 | AP | 1 | 5c6f7cd8ea54… |
| 2022-06-29 02:47 UTC · 2 captures of this ZIP | 2022-06 | A091365-002 | AP | 1 | 5c6f7cd8ea54… |
| 2022-04-08 23:34 UTC | 2022-04 | A091365-001 | AP | 1 | 5d02ea3f76ae… |
| 2022-04-08 23:34 UTC | 2022-04 | A091365-002 | AP | 1 | 5d02ea3f76ae… |
| 2022-04-04 05:41 UTC | 2022-04 | A091365-001 | AP | 1 | 4b0b4de00fa7… |
| 2022-04-04 05:41 UTC | 2022-04 | A091365-002 | AP | 1 | 4b0b4de00fa7… |
| 2019-12-13 00:20 UTC | 2019-12 | A091365-001 | AP | 1 | 74a2ff9319b5… |
| 2019-12-13 00:20 UTC | 2019-12 | A091365-002 | AP | 1 | 74a2ff9319b5… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| gemcitabine | GEMCITABINE | Dr. Reddy's Laboratories Limited | eafcebc8-ddef-bb6b-fd0a-9d8b9962cdc4 | 2024-09-09 | Warnings, Adverse reactions | 55111-686-07 55111-687-25 55111-686 55111-687 55111068725 55111068607 12d7e1d6-334a-7d1c-2db2-ea73c496d9ff eafcebc8-ddef-bb6b-fd0a-9d8b9962cdc4 |
Adverse event summaries are temporarily unavailable. Other product information remains available.