Gemcitabine 38 mg/mL Injection, Solution, 1 vial
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Nucleoside Metabolic Inhibitor class.
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🩺 Clinical
- Gemcitabine is used for several different cancers depending on which form you receive. The IV injection (brands include Avgemsi and Gemcitabine) treats pancreatic cancer, non-small...
- Common side effects include nausea, vomiting, fatigue from low red blood cells, fever, and skin rash. Your care team will regularly check your blood counts because gemcitabine can...
- What side effects should I expect, and which ones mean I need to call my doctor right away?
- No — gemcitabine can seriously harm or kill an unborn baby, so it must not be used during pregnancy. If you are a woman of childbearing age, you'll need to use reliable contracepti...
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Supplement & herbal interactions
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
3 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $1.52 | $8.01 / 5.26 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9201 | $2.884 / J9201 unit | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Gemcitabine 38 mg/mLthis 71288-0117-06 | Meitheal | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
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🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 71288-0117-06 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-06) / 5.26 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
| 71288-0117-28 | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-28) / 26.3 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
| 71288-0117-54 | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-54) / 52.6 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
| 71288-0117-91 | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-91) / 5.26 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
| 71288-0117-92 | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-92) / 26.3 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
| 71288-0117-93 | 1 VIAL, SINGLE-DOSE in 1 CARTON (71288-117-93) / 52.6 mL in 1 VIAL, SINGLE-DOSE | 2020-12-11 | Active |
This pack accounts for about 25% of this product's recent Medicaid fills; the largest share goes to a different pack size. See all packs ↓
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Gemcitabine 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 )
1.1Ovarian Cancer Gemcitabine 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.
1.2Breast Cancer Gemcitabine 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.
1.3Non-Small Cell Lung Cancer Gemcitabine 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).
1.4Pancreatic Cancer Gemcitabine 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 Injection is indicated for patients previously treated with fluorouracil.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Gemcitabine injection is for intravenous use only. Ovarian Cancer: 1,000 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.1 ) Breast Cancer: 1,250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle.
( 2.2 ) Non-Small Cell Lung Cancer: 1,000 mg/m 2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle or 1,250 mg/m 2 over 30 minutes on Days 1 and 8 of each 21-day cycle. ( 2.3 ) Pancreatic Cancer: 1,000 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 )
2.1Ovarian Cancer Recommended Dose and Schedule The recommended dosage of gemcitabine injection is 1,000 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 injection administration. Refer to carboplatin prescribing information for additional information. Dosage Modifications Recommended dosage modifications for gemcitabine injection 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 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 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 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 injection dose to 800 mg/m 2 on Day 1 only
2.2Breast Cancer Recommended Dose and Schedule The recommended dosage of gemcitabine injection is 1,250 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 injection administration. Refer to paclitaxel prescribing information for additional information. Dosage Modifications Recommended dosage modifications for gemcitabine injection 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 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
2.3Non-Small Cell Lung Cancer Recommended Dose and Schedule 28-day schedule The recommended dosage of gemcitabine injection is 1,000 mg/m 2 intravenously over 30 minutes on Days 1, 8, and 15 of each 28-day cycle in combination with cispl…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 200 mg per 5.26 mL (38 mg per mL), 1 gram per 26.3 mL (38 mg per mL), and 2 grams per 52.6 mL (38 mg per mL) as a clear and colorless to light straw-colored solution in a single-dose vial. Injection: 200 mg per 5.26 mL (38 mg per mL), 1 gram per 26.3 mL (38 mg per mL), or 2 grams per 52.6 mL (38 mg per mL) in a single-dose vial. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Gemcitabine 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 Cautions ▾
5 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 ) Severe Cutaneous Adverse Reactions (SCARs): Permanently discontinue gemcitabine injection if SCARs occur.
( 5.3 ) Pulmonary Toxicity and Respiratory Failure: Discontinue gemcitabine 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 HUS or severe renal impairment.
( 5.5 ) Hepatic Toxicity: Monitor hepatic function prior to initiation and during treatment. Discontinue gemcitabine 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.
( 5.9 ) Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue gemcitabine. ( 5.10 )
5.1Schedule-Dependent Toxicity In clinical trials evaluating the maximum tolerated dose of gemcitabine, 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 is influenced by the length of the infusion [see Clinical Pharmacology ( 12.3 )] . Refer to the recommended gemcitabine injection dosage [see Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 )] .
5.2Myelosuppression Myelosuppression manifested by neutropenia, thrombocytopenia, and anemia, occurs with gemcitabine as a single agent and the risks are increased when gemcitabine 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. 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 in combination with another drug [see Adverse Reactions ( 6.1 )] .
Prior to each dose of gemcitabine 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 )] .
5.3Severe 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.
5.4Pulmonary 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 [see Adverse Reactions ( 6.1 , 6.2 )] .
Permanently discontinue gemcitabine in patients who develop unexplained dyspnea, with or without bronchospasm, or evidence of severe pulmonary toxicity.
5.5Hemolytic Uremic Syndrome Hemolytic uremic syndrome (HUS), including fatalities from renal failure or the requirement for dialysis, can…
🤒 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 .
6.1Clinical 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 as a single agent administered at doses between 800 mg/m 2 to 1,250 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 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 due to adverse reactions.
Adverse reactions resulting in discontinuation of gemcitabine in 2% of 979 patients were cardiovascular adverse reactions (myocardial infarction, cerebrovascular accident, arrhythmia, and hypertension) and adverse reactions resulting in discontinuation of gemcitabine 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 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 a a Grade based on criteria from the World Health Organization (WHO). b For approximately 60% of patients, non-laboratory adverse events were graded only if assessed to be possibly drug-related. c N=699-974; all patients with laboratory or non-laboratory data. Adverse Reactions b Gemcitabine 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 Table 6: Selected Laboratory Abnormalities Occurring in Patients Receiving Single Agent Gemcitabine a a Grade based on criteria from WHO. b Regardless of causality. c N=699-974; all patients with laboratory or non-laboratory data.
Laboratory Abnormality…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary Based on animal data and its mechanism of action, gemcitabine 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 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 Specific 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 malformations (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day [about 0.005 times the 1,000 mg/m 2 clinical dose based on body surface area (BSA)]. Gemcitabine is 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 (about 0.002 times the 1,000 mg/m 2 clinical dose based on BSA).
8.2Lactation Risk Summary There is no information regarding the presence of gemcitabine 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, advise women not to breastfeed during treatment with gemcitabine and for at least one week following the last dose.
8.3Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating gemcitabine [see Use in Specific Populations ( 8.1 )] . Contraception Gemcitabine 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 and for 6 months after the final dose.
Males Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with gemcitabine and for 3 months after the final dose [see Nonclinical Toxicology ( 13.1 )] . Infertility Males Based on animal studies, gemcitabine may impair fertility in males of reproductive potential [see Nonclinical Toxicology ( 13.1 )]. It is not known whether these effects on fertility are reversible.
8.4Pediatric Use The safety and effectiveness of gemcitabine 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 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.
8.5Geriatric Use In clinical studies which enrolled 979 patients with various malignancies who received single agent gemcitabine, no overall differences in safety were observed between patients aged…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on animal data and its mechanism of action, gemcitabine 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 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 Specific 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 malformations (cleft palate, incomplete ossification) at doses of 1.5 mg/kg/day [about 0.005 times the 1,000 mg/m 2 clinical dose based on body surface area (BSA)]. Gemcitabine is 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 (about 0.002 times the 1,000 mg/m 2 clinical dose based on BSA).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of gemcitabine 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 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.
🧓 Geriatric Use ▾
8.5Geriatric Use In clinical studies which enrolled 979 patients with various malignancies who received single agent gemcitabine, 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 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 clearance is affected by age; however, there are no recommended dose adjustments based on patients' age [see Clinical Pharmacology ( 12.3 )] .
🆘 Overdosage ▾
10 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 5,700 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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.
12.3Pharmacokinetics 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 dose varied from 500 mg/m 2 to 3,600 mg/m 2 .
Distribution The volume of distribution was increased with infusion length. Volume of distribution of gemcitabine was 50 L/m 2 following infusions lasting <70 minutes. For long infusions, the volume of distribution rose to 370 L/m 2 .
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 1,000 mg/m 2 of radiolabeled drug as a 30-minute infusion.
Within one (1) 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. 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 .
Table 15: Gemcitabine Clearance and Half-Life for the “Typical” Patient a Half-life for patients receiving a <70 minute infusion. Age Clearance Men (L/hr/m 2 ) Clearance Women (L/hr/m 2 ) Half-Life a Men (min) Half-Life a 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 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 wi…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Gemcitabine Injection is a clear and colorless to light straw-colored solution, free of visible particulate matter, and is available in sterile single-dose vials individually packaged in a carton containing: NDC Gemcitabine Injection (38 mg per mL) Package Factor 71288- 117 -06 200 mg per 5.26 mL, sterile solution in a single-dose glass vial 1 vial per carton 71288- 117 -28 1 gram per 26.3 mL, sterile solution in a single-dose glass vial 1 vial per carton 71288- 117 -54 2 grams per 52.6 mL, sterile solution in a single-dose glass vial 1 vial per carton Storage Conditions Store refrigerated between 2° and 8°C (36° and 46°F).
Do not freeze . Gemcitabine Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.
1 Discard unused portion. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.
📦 Storage and Handling ▾
Storage Conditions Store refrigerated between 2° and 8°C (36° and 46°F). Do not freeze . Gemcitabine Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Discard unused portion. Sterile, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex.
📋 Description ▾
11 DESCRIPTION Gemcitabine is a nucleoside metabolic inhibitor. The chemical name of gemcitabine HCl is 2′-deoxy- 2′,2′-difluorocytidine monohydrochloride (β-isomer). The structural formula is as follows: Gemcitabine HCl is a white to off-white solid with a molecular formula of C 9 H 11 F 2 N 3 O 4 • HCl and a molecular weight of 299.66 g/mol.
It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents. Gemcitabine Injection is a sterile solution in single-dose vials for intravenous use. Each vial contains 200 mg, 1 gram, or 2 grams of gemcitabine equivalent to 227.55 mg, 1.14 grams, or 2.28 grams of gemcitabine HCl.
Each mL contains 38 mg of gemcitabine free base in Water for Injection equivalent to 43.26 mg of gemcitabine HCl. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment. Structural Formula
💬 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 can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with gemcitabine 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 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 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 [see Use in Specific Populations ( 8.3 ), Nonclinical Toxicology ( 13.1 )] .
This product’s labeling may have been updated. For the most recent prescribing information, please visit www.meithealpharma.com. meitheal ® Mfd. for Meitheal Pharmaceuticals Chicago, IL 60631 (USA) ©2024 Meitheal Pharmaceuticals Inc. Mfd. by Kindos Pharmaceuticals Co., Ltd.
Chengdu, China 611731 Revised: August 2024