Gemcitabine Injection
Generic: GEMCITABINE HYDROCHLORIDE
Gemcitabine Injection
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Identification
GEMCITABINE HYDROCHLORIDE
GEMCITABINE
Meitheal Pharmaceuticals Inc.
HUMAN PRESCRIPTION DRUG
Administration
INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
INTRAVENOUS
ANDA091365
Active Ingredients
| Ingredient | Strength |
|---|---|
| GEMCITABINE HYDROCHLORIDE | 200 mg/1 |
Pharmacological Class
Data sourced from openFDA / DailyMed. For full prescribing information, consult the drug label.
Wholesale compliance resources
Clinical Drug Information
Indications & Usage
1 INDICATIONS AND USAGE Gemcitabine for injection is a nucleoside metabolic inhibitor indicated: in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. ( 1.1 ) in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. ( 1.2 ) in combination with cisplatin, for the treatment of non-small cell lung cancer. ( 1.3 ) as a single agent for the treatment of pancreatic cancer. ( 1.4 ) 1.1 Ovarian Cancer 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. 1.2 Breast Cancer 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. 1.3 Non-Small Cell Lung Cancer 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). 1.4 Pancreatic Cancer 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.
Dosage & Administration
2 DOSAGE AND ADMINISTRATION Gemcitabine for injection is for intravenous use only. Ovarian Cancer: 1000 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.1 ) Breast Cancer: 1250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.2 ) Non-Small Cell Lung Cancer: 1000 mg/m 2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle or 1250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.3 ) Pancreatic Cancer: 1000 mg/m 2 over 30 minutes once weekly for the first 7 weeks, then one week rest, then once weekly for 3 weeks of each 28-day cycle. ( 2.4 ) 2.1 Ovarian Cancer 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 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 )]. Table 1: Recommended Dosage Modifications for Gemcitabine For Injection for Myelosuppression on Day of Treatment in Ovarian Cancer Treatment Day Absolute Neutrophil Count (x 10 6 /L) Platelet Count (x 10 6 /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 Table 2: Recommended Dosage Modifications for Gemcitabine For Injection for Myelosuppression in Previous Cycle in Ovarian Cancer Occurrence Myelosuppression During Treatment Cycle Dosage Modification Initial Occurrence Absolute neutrophil count less than 500 x 10 6 /L for more than 5 days or Absolute neutrophil count less than 100 x 10 6 /L for more than 3 days or Febrile neutropenia or Platelets less than 25,000 x 10 6 /L or Cycle delay for more than one week due to toxicity Permanently reduce gemcitabine for injection to 800 mg/m 2 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/m 2 on Day 1 only 2.2 Breast Cancer Recommended Dose and Schedule The recommended dosage of gemcitabine for injection is 1250 mg/m 2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with paclitaxel 175 mg/m 2 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 )] . Table 3: Recommended Dosage Modifications for Gemcitabine For Injection for Myelosuppression on Day of Treatment in Breast Cancer Treatment Day Absolute Neutrophil Count (x 10 6 /L) Platelet Count (x 10 6 /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 2.3 Non-Small Cell Lung Cancer Recommended Dose and Schedule 28-day schedule The recommended dosage of gemcitabine for injection is 1000 mg/m 2 intravenously over 30 minutes on Days 1, 8, and 15 of each 28-day cycle in combination with cisplatin 100 mg/m 2 administered intravenously on Day 1 after gemcitabine for injection administration. 21-day schedule The recommended dosage of gemcitabine for injection is 1250 mg/m 2 intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle in combination with cisplatin 100 mg/m 2 administered intravenously on Day 1 after gemcitabine for injection administration. Refer to cisplatin prescribing information for additional information. Dosage Modifications Recommended dosage modifications for gemcitabine for injection 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 )] . 2.4 Pancreatic Cancer Recommended Dose and Schedule The recommended dosage of gemcitabine for injection is 1000 mg/m 2 intravenously over 30 minutes. The recommended treatment schedule is as follows: Weeks 1 to 8: weekly dosing for the first 7 weeks followed by one week rest. After week 8: weekly dosing on Days 1, 8, and 15 of each 28-day cycle. 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 )] . Table 4: Recommended Dosage Modifications for Gemcitabine For Injection for Myelosuppression in Pancreatic Cancer and Non-Small Cell Lung Cancer Absolute Neutrophil Count (x 10 6 /L) Platelet Count (x 10 6 /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 2.5 Dosage Modifications for Non-Hematologic Adverse Reactions Permanently discontinue gemcitabine for injection for any of the following: Severe Cutaneous Adverse Reactions (SCARs) [see Warnings and Precautions ( 5.3 )] Unexplained dyspnea or evidence of severe pulmonary toxicity [see Warnings and Precautions ( 5.4 )] Hemolytic-uremic syndrome (HUS) or severe renal impairment [see Warnings and Precautions ( 5.5 )] Severe hepatic toxicity [see Warnings and Precautions ( 5.6 )] Capillary leak syndrome (CLS) [see Warnings and Precautions ( 5.7 )] Posterior reversible encephalopathy syndrome (PRES) [see Warnings and Precautions ( 5.10 )] 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. 2.6 Preparation Gemcitabine for injection vials contain no antimicrobial preservatives and are intended for single use only. Gemcitabine for injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Exercise caution and wear gloves when preparing gemcitabine for injection solutions. Immediately wash the skin thoroughly or rinse the mucosa with copious amounts of water if gemcitabine for injection contacts the skin or mucus membranes. Death has occurred in animal studies due to dermal absorption. Reconstitute the 200 mg vial with 5 mL and the 1 g vial with 25 mL of 0.9% Sodium Chloride Injection, USP to yield a gemcitabine for injection concentration of 38 mg/mL. Reconstituted gemcitabine for injection is a clear, colorless to light straw-colored solution. Visually inspect reconstituted product for particulate matter and discoloration. Discard if particulate matter or discoloration is observed. Withdraw the calculated dose from the vial and discard any unused portion. Prior to administration, dilute the reconstituted solution with 0.9% Sodium Chloride Injection, USP to a minimum final concentration of at least 0.1 mg/mL. Store gemcitabine solutions (reconstituted and diluted) at controlled room temperature of 20°C to 25°C (68°F to 77°F). Do not refrigerate as crystallization can occur. Discard gemcitabine solutions if not used within 24 hours after reconstitution. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.
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 Meitheal Pharmaceuticals Inc. at 1-844-824-8426 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 for injection 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 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 10% of Patients Receiving Gemcitabine with Carboplatin and at Higher Incidence than in Patients Receiving Single Agent Carboplatin [Between Arm Difference of ≥5% (All Grades) or ≥2% (Grades 3-4)] in Study 1 a a Grade based on National Cancer Institute CTC Version 2.0. b Regardless of causality. Adverse Reactions b 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 10% of Patients Receiving Gemcitabine with Paclitaxel and at a Higher Incidence than Patients Receiving Single Agent Paclitaxel [Between Arm Difference of ≥5% (All Grades) or ≥2% (Grades 3-4)] in Study 2 a a Grade based on National Cancer Institute CTC Version 2.0. b Regardless of causality. Laboratory Abnormality b 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 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 10% of Patients Receiving Gemcitabine with Cisplatin and at Higher Incidence than in Patients Receiving Single Agent Cisplatin [Between Arm Difference of ≥5% (All Grades) or ≥2% (Grades 3-4)] in Study 3 a a Grade based on National Cancer Institute CTC. b Regardless of causality. c N=217-253; all gemcitabine for injection/cisplatin patients with laboratory or non-laboratory data d N=213-248; all cisplatin patients with laboratory or non-laboratory data e Percent of patients receiving transfusions. Percent transfusions are not CTC-graded events. Laboratory Abnormality b Gemcitabine For Injection/Cisplatin c Cisplatin d 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 Transfusions e 39 - - 13 - - Platelet Transfusions e 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. Table 13: Selected Adverse Reactions in Patients Receiving Gemcitabine with Cisplatin in Study 4 a a Grade based on criteria from the WHO. b Non-laboratory events were graded only if assessed to be possibly drug-related. Pain data were not collected. c N=67-69; all gemcitabine for injection/cisplatin patients with laboratory or non-laboratory data. d N=57-63; all Etoposide/cisplatin patients with laboratory or non-laboratory data. e Flu-like syndrome and edema were not graded. Adverse Reactions b Gemcitabine For Injection/Cisplatin c Etoposide/Cisplatin d 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 Edema e 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 Syndrome e 3 - - 0 - - Dyspnea 1 0 1 3 0 0 Table 14: Selected Laboratory Abnormalities Occurring in Patients Receiving Gemcitabine with Cisplatin in Study 4 a a Grade based on criteria from the WHO. b Regardless of causality. c N=67-69; all gemcitabine for injection/cisplatin patients with laboratory or non-laboratory data. d N=57-63; all Etoposide/cisplatin patients with laboratory or non-laboratory data. e WHO grading scale not applicable to proportion of patients with transfusions. Laboratory Abnormality b Gemcitabine For Injection/Cisplatin c Etoposide/Cisplatin d 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 Transfusions c 29 - - 21 - - Platelet Transfusions e 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 6.2 Postmarketing Experience 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. Blood and lymphatic system: Thrombotic microangiopathy (TMA) Cardiovascular : Congestive heart failure, myocardial infarction, arrhythmias, supraventricular arrhythmias Vascular : Peripheral vasculitis, gangrene, capillary leak syndrome Skin : Cellulitis; pseudocellulitis; severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP); desquamation and bullous skin eruptions Hepatic : Hepatic failure, hepatic veno-occlusive disease Pulmonary : Interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, adult respiratory distress syndrome (ARDS), pulmonary eosinophilia Nervous System : Posterior reversible encephalopathy syndrome (PRES)
Information for Patients
17 PATIENT COUNSELING INFORMATION 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 )] . Infertility Advise males of reproductive potential of the potential for reduced fertility with gemcitabine for injection [see Use in Specific Populations ( 8.3 ), Nonclinical Toxicology ( 13.1 )] . meitheal® Mfd. for Meitheal Pharmaceuticals Chicago, IL 60631 (USA) ©2024 Meitheal Pharmaceuticals Inc. Mfd. by Kindos Pharmaceuticals Co., Ltd. Chengdu, China 611731 Revised: October 2024 LB-181-V5
Clinical data sourced from openFDA drug labeling. For complete prescribing information, consult the full drug label.