Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 200mg/single-use vial (Gemzar, generics)
- 1g/single-use vial (Gemzar, generics)
solution for injection (generics)
- 200mg/2mL (100mg/mL)
- 200mg/5.26mL (38mg/mL)
- 1g/10mL (100mg/mL)
- 1g/26.3mL (38mg/mL)
- 1.5g/15mL (100mg/mL)
- 2g/20mL (100mg/mL)
- 2g/52.6mL (38mg/mL)
injection, single-dose premixed infusion bag (Infugem)
- 10mg/mL (contains gemcitabine in 0.9% NaCl) concentration in following sizes:
- 1200mg/120mL
- 1300mg/130mL
- 1400mg/140mL
- 1500mg/150mL
- 1600mg/160mL
- 1700mg/170mL
- 1800mg/180mL
- 1900mg/190mL
- 2000mg/200mL
- 2200mg/220mL
Pancreatic Cancer
Indicated as a single-agent for pancreatic cancer
1000 mg/m² IV infusion over 30 min once weekly x 7 weeks; rest 1 week, THEN
1000 mg/m² IV once weekly for 3 weeks of each 28-day cycle
Various regimens exist including monotherapy and in combination with other chemotherapy agents (eg, erlotinib, paclitaxel protein bound, capecitabine)
Also see Administration
Non-small Cell Lung Cancer
Indicated in combination with cisplatin for non-small cell lung cancer
1000 mg/m² IV infusion over 30 minutes on days 1, 8, and 15 of each 28-day cycle, OR
1250 mg/m² IV infusion over 30 minutes on days 1 and 8 of each 21-day cycle
Administer cisplatin 100 mg/m² IV after gemcitabine on day 1
Also see Administration
Breast Cancer
Indicated 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
1250 mg/m² IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle
With paclitaxel 175 mg/m² on Day 1 as a 3 hr infusion before gemcitabine
Also see Administration
Ovarian Cancer
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
1000 mg/m² IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle
With carboplatin AUC 4 on Day 1 after gemcitabine
Also see Administration
Dosage Modifications
Myelosuppression (ovarian cancer)
- Day 1
- Absolute neurophil count (ANC) ≥1,500 x 10^6/L AND platelet count ≥100,000 x 10^6/L: No dosage adjustment necessary
- ANC <1,500 x 10^6/L OR platelets <100,000 x 10^6/L: Delay treatment
- Day 8
- ANC≥1,500 x 10^6/L AND platelets ≥100,000 x 10^6/L: No dosage adjustment necessary
- ANC 1,000 to 1499 x 10^6/L OR platelets 75,000 to 99,999 x 10^6/L: 50% of the full dose
- ANC <1,000 x 10^6/L OR platelets <75,000 x 10^6/L: Hold treatment
- Initial or subsequent occurrences
- ANC <500 x 10^6/L for more than 5 days OR
- ANC <100 x 10^6/L for more than 3 days OR
- Febrile neutropenia OR
- Platelets <25,000 x 10^6/L OR
- Cycle delay of more than 1 week due to toxicity
- If any of the above toxicities occur after the initial dose reduction, permanently reduce dose to 800 mg/m² on Days 1 and 8
Myelosuppression (breast cancer)
- Day 1
- ANC ≥1,500 x 10^6/L AND platelet count ≥100,000 x 10^6/L: No dosage adjustment necessary
- ANC <1,500 x 10^6/L OR platelets <100,000 x 10^6/L: Hold treatment
- Day 8
- ANC≥1,200 x 10^6/L AND platelets ≥75,000 x 10^6/L: No dosage adjustment necessary
- ANC 1,000 to 1199 x 10^6/L OR platelets 50,000 to 75,000 x 10^6/L: 75% of the full dose
- ANC 700 to 999 x 10^6/L AND platelets ≥50,000 x 10^6/L: 50% of the full dose
- ANC <700 x 10^6/L OR platelets <50,000 x 10^6/L: Hold treatment
Myelosuppression (non-small cell lung cancer or pancreatic cancer)
- ANC ≥1,000 x 10^6/L AND platelets ≥100,000 x 10^6/L: No dosage adjustment necessary
- ANC 500 to 999 x 10^6/L OR platelets 50,000 to 99,999 x 10^6/L: 75% of the full dose
- ANC <500 x 10^6/L OR platelets ≥50,000 x 10^6/L: Hold treatment
Non-hematologic adverse reactions
- Permanently discontinue for any of the following:
- Unexplained dyspnea or other evidence of severe pulmonary toxicity
- Hemolytic uremic syndrome
- Severe hepatic toxicity
- Capillary leak syndrome
- Posterior reversible encephalopathy syndrome
- Other severe (Grade 3 or 4) non-hematological toxicity: Withhold or reduce dose by 50% until resolved
- No dose modifications are recommended for alopecia, nausea, or vomiting
Dosing Considerations
Premix bag only: Select the premixed bag that allow for a variance of up to 5% of the BSA-calculated dose (see Administration)
Bladder Cancer (Off-label)
May be considered for muscle-invasive bladder cancer in combination with cisplatin
Cholangiocarcinoma (Orphan)
Orphan designation for treatment of cholangiocarcinoma
Sponsor
- InnoPharmax, Inc; 9F, No. 22, Lane 478, Rueiguang Road; Taipei
Safety and efficacy not established
In clinical studies, patients with various cancers who received gemcitabine as a single agent had 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, there was significantly higher Grade 3/4 neutropenia in women 65 years of age or older
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
N/V (69%)
Anemia (65%)
Elev LFTs (68%)
Neutropenia (63%)
Leukopenia (62%)
Pain (48%)
Proteinuria (45%)
Fever (41%)
Hematuria (35%)
Rash (30%)
Thrombocytopenia (24%)
Dyspnea (23%)
Constipation (23%)
Diarrhea (19%)
Flu-like syndrome (19%)
Hemorrhage (17%)
BUN increased (16%)
Infection (16%)
Alopecia (15%)
Edema (13%)
Elev bilirubin (13%)
1-10%
Paresthesia (2-10%)
Creatinine increased (2-8%)
Inj site reactions (4%)
Bronchospasm (2%)
Postmarketing Reports
Cardiovascular: CHF, MI, arrhythmias, supraventricular arrhythmias
Vascular disorders: Peripheral vasculitis, gangrene, capillary leak syndrome
Skin: Cellulitis, pseudocellulitis, severe skin reactions, including desquamation and bullous skin eruptions
Hepatic: Hepatic failure, hepatic veno-occlusive disease
Pulmonary: Interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, ARDS
Pulmonary: Pulmonary eosinophilia
Blood and lymphatic system: Thrombotic microangiopathy
Warnings
Contraindications
Hypersensitivity
Cautions
Serious cases of thrombotic microangiopathy reported
In combination with carboplatin or paclitaxel: patients should have ANC >1.5 x 10^6/mL and platelet count >10^8/mL prior to each cycle
Capillary leak syndrome reported with severe consequences; discontinue if symptoms occur
Pulmonary toxicity, including interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, and ARDS reported; onset of pulmonary symptoms may occur up to 2 weeks after last dose; discontinue treatment in patients who develop unexplained dyspnea, with or without bronchospasm, or have any evidence of pulmonary toxicity
Assess renal function prior to initiation of therapy and periodically during treatment; hemolytic uremic syndrome reported, including fatalities; permanently discontinue therapy in patients with HUS or severe renal impairment; renal failure may not be reversible even with discontinuation of therapy
Drug-induced liver injury reported, including liver failure and death; assess hepatic function prior to initiation of therapy and periodically during treatment; discontinue drug in patients that develop severe liver injury
Not indicated for use with radiation therapy; know to exacerbate radiation toxicity, including life-threatening mucositis, especially esophagitis and pneumonitis; excessive toxicity not observed when treatment is administered more than 7 days before or after radiation; radiation recall has been reported in patients who received drug after prior radiation
Infusions longer than 60 minutes or more frequently than qWk increase the incidence of clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia; gemcitabine half-life is influenced by the length of the infusion
Posterior reversible encephalopathy syndrome (PRES) reported; PRES can present with headache, seizure, lethargy, hypertension, confusion, blindness, and other visual and neurologic disturbances; discontinue if PRES develops
Advise females of reproductive potential to use effective contraception during treatment and for 6 months after final dose; advise male patients with female partners of reproductive potential to use effective contraception during and for 3 months following final dose
Myelosuppression
- In patients who received single- agent therapy, Grade 3-4 neutropenia, anemia, and thrombocytopenia reported in 25%, 8%, and 5%, respectively
- In patients receiving gemcitabine in combination with another drug Grade 3-4 neutropenia, anemia, and thrombocytopenia varied from 48% to 71%, 8% to 28%, and 5% to 55%, respectively
- Obtain a complete blood count (CBC) with a differential and a platelet count prior to each dose of Gemcitabine Injection; modify dosage as recommended
Pregnancy & Lactation
Pregnancy
Based on animal data and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; therapy is expected to result in adverse reproductive effects; drug was teratogenic, embryotoxic, and fetotoxic in mice and rabbits; advise pregnant women of potential risk to a fetus
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for 6 months after final dose
- Advise male patients with female partners of reproductive potential to use effective contraception during and for 3 months following final dose
Infertility
- Based on animal studies, Gemcitabine Injection may impair fertility in males of reproductive potential
Pregnancy Testing
- Verify pregnancy status in females of reproductive potential prior to initiating therapy
Contraception
- Therapy can cause fetal harm when administered to a pregnant woman
Females
- Because of potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment and for 6 months after final dose
Males
- Because of potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after final dose
Lactation
There are no data on presence of drug in human milk, or effects of gemcitabine on breastfed infant or milk production; because of potential for serious adverse reactions in nursing infants from therapy, advise a lactating woman not to breastfeed during treatment and for one week after the final dose
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Pyrimidine analog; inhibits DNA synthesis by inhibiting the ribonucleotide reductase, cell cycle-specific for the S-phase of the cycle (also blocks cellular progression at G1/S-phase)
Metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides
Gemcitabine diphosphate inhibits ribonucleotide reductase, resulting in reductions in deoxynucleotide concentrations, including dCTP
Gemcitabine triphosphate competes with dCTP for incorporation into DNA; 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
Distribution
Vd was increased with infusion length
Vd: 50 L/m² (following infusions lasting <70 minutes); 370 L/m² (long infusions)
Metabolism
Active metabolite, gemcitabine triphosphate, can be extracted from peripheral blood mononuclear cells
Elimination
Excretion: Urine (92-98%)
Half-life: 1.7-19.4 hr
Clearance
- Male: 92.2 L/hr/m² (29 years); 75.7 L/hr/m² (45 years); 55.1 L/hr/m² (65 years); 40.7 L/hr/m² (79 years)
- Female: 69.4L/hr/m² (29 years); 57 L/hr/m² (45 years); 41.5 L/hr/m² (65 years); 30.7 L/hr/m² (79 years)
Administration
IV Incompatibilities
Y-site: acyclovir, amphotericin B, cefoperazone, cefotaxime, furosemide, ganciclovir, imipenem/cilastatin, irinotecan, methotrexate, methylprednisolone sodium succinate, mitomycin, piperacillin, piperacillin/tazobactam, prochlorperazine
IV Compatibilities
Y-site (partial list): ampicillin, carboplatin, cefazolin, chlorproazine, cimetidine, clindamycin, cytarabine, diphenhydramine, dopamine, etoposide, heparin, linezolid, metoclopramide, morphine, paclitaxel, KCl, NaHCO3, topotecan, vancomycin, zidovudine
IV Preparation
Follow guidelines for handling and disposal of chemotherapeutic agents
Lyophilized powder
- Reconstitute 200 mg vial with 5 mL 0.9% NaCl or 1000 mg vial with 25 mL 0.9% NaCl
- Resulting solution is 38 mg/mL
- The appropriate dose may be further diluted with 0.9% NaCl to concentrations as low as 0.1 mg/mL
Solution for injection (from either 38 mg/mL or 100 mg/mL vials)
- Inspect solution and discard vial if particulate matter or discoloration is observed
- Dilute with 0.9% NaCl to concentrations as low as 0.1 mg/mL
- Do not shake; mix diluted solution by gentle inversion
Premixed Bag
- Infusion bag selection
- Premixed bags are ready for infusion and do not require any further preparation prior to use
- Do not dilute prior to use
- Do not remove or add medication
- Select premixed bag(s) for infusion based on the patient’s BSA range as outlined below in the prescribing information
- Administered dose may vary from the BSA-calculated dose by no more than 5%
IV Administration
For IV infusion only
Solution for injection (ie, 38 mg/mL, 100 mg/mL) must be diluted before IV administration
Infuse IV over 30 min
Avoid rapid infusions
IV Administration (Premixed Bag)
Infuse over 30 minutes
If two premixed infusion bags are required, infuse the total volume of both bags over 30 minutes.
Remove overwrap; check for leaks by squeezing the inner bag firmly
If leaks are found, discard the bag
Injection is a clear, colorless solution
Visually inspect for any particulate matter or discoloration prior to use
Discard if particulate matter or discoloration is found
Follow applicable special handling and disposal procedures; exercise caution and wear gloves when handling drug; immediately wash the skin thoroughly or rinse the mucosa with copious amounts of water if drug contacts the skin or mucus membranes
Death has occurred in animal studies due to dermal absorption
Storage
Lyophilized powder
- Unopened vials: Store at room temperature 20-25°C (68-77°F)
- Reconstituted solution: Store at room temperature for up to 24 hr; do NOT refrigerate (crystallization can occur)
Solution for injection
- 38 mg/mL
- Unopened vials: Refrigerate at 2-8°C (36-46°F)
- Do not freeze
- 100 mg/mL
- Crystallization can occur if refrigerated
- Unopened vials: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
- After initial withdrawal with a needle, the remaining portion in the vial may be stored at room temperature and should be used or discarded within 28 days
- Diluted solution (from either 38 mg/mL or 100 mg/mL vials)
- Store at controlled room temperature for up to 24 hr; do NOT refrigerate
Premixed bag
- Unopened infusion bags: Stable until the expiration date indicated on the package when stored at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F); do not freeze as crystallization can occur
Images
Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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