Gemcitabine hydrochloride
Injection, Powder, Lyophilized, For Solution · Intravenous
Uses
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. Gemciatbine is indicated for patients previously treated with fluorouracil.
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 25,000x10 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) ] .
Dosage forms and strengths
For injection: 200 mg gemcitabine or 1 g gemcitabine as a sterile white to off-white lyophilized powder in a single-dose vial for reconstitution. For injection: 200 mg or 1 gram lyophilized powder in single-dose vials for reconstitution. ( 3 )
Contraindications
Gemcitabine for Injection is contraindicated in patients with a known hypersensitivity to gemcitabine. Reactions include anaphylaxis [see Adverse Reactions (6.1) ] . Patients with a known hypersensitivity to gemcitabine. ( 4 )
Warnings and precautions
Schedule-Dependent Toxicity: Increased toxicity with infusion time greater than 60 minutes or dosing more frequently than once weekly. ( 5.1 ) Myelosuppression: Monitor for myelosuppression prior to each cycle and reduce or withhold dose for severe myelosuppression. ( 5.2 , 5.7 ) Severe Cutaneous Adverse Reactions (SCARs): Permanently discontinue gemcitabine injection if SCARs occur. ( 5.3 ) Pulmonary Toxicity and Respiratory Failure: Discontinue Gemcitabine for Injection for unexplained dyspnea or other evidence of severe pulmonary toxicity. ( 5.4 ) Hemolytic Uremic Syndrome (HUS): Monitor renal function prior to initiation and during treatment. Discontinue Gemcitabine for Injection for HUS or severe renal impairment. ( 5.5 ) Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment. Discontinue Gemcitabine for Injection for severe hepatic toxicity. ( 5.6 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females and males of reproductive potential to use effective contraception. ( 5.7 , 8.1 ) Exacerbation of Radiation Therapy Toxicity: May cause severe and life-threatening toxicity when administered during or within 7 days of radiation therapy. ( 5.8 ) Capillary Leak Syndrome: Discontinue Gemcitabine for Injection ( 5.9 ) Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue Gemcitabine for Injection. ( 5.10 ) 5.1 Schedule-Dependent Toxicity 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 )] . 5.2 Myelosuppression 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 )] . 5.3 Severe Cutaneous Adverse Reactions (SCARs) SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, 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. 5.4 Pulmonary Toxicity and Respiratory Failure 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. 5.5 Hemolytic Uremic Syndrome 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. 5.6 Hepatic Toxicity 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. 5.7 Embryo-Fetal 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.
Side effects
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 Teyro Labs Private Limited at 1800-726-4148 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 <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. Table 5: Selected Adverse Reactions Occurring in ≥10% of Patients Receiving Single Agent Gemcitabine for Injection a Adverse Reactions b Gemcitabine for Injection c 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 a Grade based on criteria from the World Health Organization (WHO). b For approximately 60% of patients, non-laboratory adverse reactions were graded only if assessed to be possibly drug-related. c N=699-974; all patients with laboratory or non-laboratory data. Table 6: Selected Laboratory Abnormalities Occurring in Patients Receiving Single Agent Gemcitabine for Injection a Laboratory Abnormality b Gemcitabine for Injection c 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 a Grade based on criteria from the WHO. b Regardless of causality. c N=699-974; all patients with laboratory or non-laboratory data. Additional adverse reactions include the following: Transfusion requirements: Red blood cell transfusions (19%); platelet transfusions (<1%) Edema: Edema (13%), peripheral edema (20%), generalized edema (<1%) Flu-like symptoms: Fever, asthenia, anorexia, headache, cough, chills, myalgia, asthenia insomnia, rhinitis, sweating and/or malaise (19%) Infection: Sepsis (<1%) Extravasation: Injection-site reactions (4%) Allergic: Bronchospasm (<2%); anaphylactoid reactions 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.
Use in specific populations
Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy 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/m 2 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/m 2 clinical dose based on BSA). 8.2 Lactation 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. 8.3 Females and Males of Reproductive Potential 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. 8.4 Pediatric Use 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/m 2 /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/m 2 /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. 8.5 Geriatric Use 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) ]. 8.6 Gender 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 )] .
Overdosage
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/m 2 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.
Description
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 C 9 H 11 F 2 N 3 O 4
• HCl. It has a molecular weight of 299.66 g/mol. Gemcitabine hydrochloride is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents. Gemcitabine for Injection a sterile white to off-white lyophilized powder and available as 200 mg and 1 g single-dose vials for intravenous use only. Each 200 mg vial contains 200 mg gemcitabine (equivalent to 227.6 mg gemcitabine hydrochloride), 200 mg mannitol and 12.5 mg sodium acetate. Each 1 g vial contains 1 g gemcitabine (equivalent to 1.138 g gemcitabine hydrochloride), 1 g mannitol, and 62.5 mg sodium acetate. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment. image description
How supplied
Gemcitabine for Injection is a sterile white to off-white lyophilized powder available in single-dose vials individually packaged in a carton containing 200 mg or 1 g gemcitabine: 200 mg vial in one carton: NDC 82511-008-20 1 g vial in one carton: NDC 82511-009-10 Gemcitabine for Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Patient 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 (5.6) , 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) ] . Manufactured by Teyro Labs Private Limited Tamil Nadu, India 601301. Revision: 09/2024
Label text from the FDA structured product label by Teyro Labs Private Limited (revised Jan 9, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Gemcitabine Hydrochloride in 4 products
Gemcitabine hydrochloride NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68083-148 | Gemcitabine Hydrochloride 200 mg/5mL Injection, Powder, Lyophilized, For Solution | Gland Pharma Limited | ANDA |
| 68083-149 | Gemcitabine Hydrochloride 1 g/25mL Injection, Powder, Lyophilized, For Solution | Gland Pharma Limited | ANDA |
| 82511-008 | Gemcitabine Hydrochloride 200 mg/5mL Injection, Powder, Lyophilized, For Solution | Teyro Labs Private Limited | ANDA |
| 82511-009 | Gemcitabine Hydrochloride 1 g/25mL Injection, Powder, Lyophilized, For Solution | Teyro Labs Private Limited | ANDA |
Frequently asked questions
What is Gemcitabine hydrochloride used for?
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,…
What are the side effects of Gemcitabine hydrochloride?
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… See the full label for the complete list.
Who makes Gemcitabine hydrochloride?
Gemcitabine hydrochloride is listed by 2 labelers in the FDA NDC directory, including Gland Pharma Limited, Teyro Labs Private Limited.