GEMCITABINE HYDROCHLORIDE
Pronounciation
Trade Name(s)
Verify pregnancy status. Baseline studies indicated; see Monitor. Review monographs of indicated antineoplastics that are to be used in combination with gemcitabine for additional information.
1,000 mg/M2 as outlined in the following treatment schedule:
Weekly dosing for the first 7 weeks followed by 1 week of rest.
Weekly dosing on Days 1, 8, and 15 of 28-day cycles.
Non–small-cell lung cancer (NSCLC):
1,000 mg/M2 as an infusion on Days 1, 8, and 15 of each 28-day cycle. Given in combination with cisplatin. Administer cisplatin 100 mg/M2 IV on Day 1 after the infusion of gemcitabine. An alternate schedule is gemcitabine 1,250 mg/M2 on Days 1 and 8 of each 21-day cycle. Administer cisplatin 100 mg/M2 IV on Day 1 after the infusion of gemcitabine.
1,250 mg/M2 as an infusion on Days 1 and 8 of each 21-day cycle. Given in combination with paclitaxel. On Day 1, administer paclitaxel 175 mg/M2 as a 3-hour infusion before the gemcitabine infusion.
1,000 mg/M2 as an infusion on Days 1 and 8 of a 21-day cycle. Given in combination with carboplatin. On Day 1 of the 21-day cycle, administer carboplatin at AUC 4 after gemcitabine administration.
1,000 mg/M2 on Days 1, 8, and 15. Repeat cycle every 28 days. Given in conjunction with cisplatin. Alternatively, 1,000 mg/M2 on Days 1 and 8. Repeat cycle every 21 days. Given in combination with carboplatin.
Hodgkin lymphoma (relapsed) or non-Hodgkin lymphoma (refractory) (unlabeled):
1,000 mg/M2 on Days 1 and 8 of a 21-day cycle. Given in combination with other agents.
Head and neck cancer (unlabeled):
1,000 mg/M2 on Days 1, 8, and 15 every 28 days or 1,000 mg/M2 on Days 1 and 8 every 21 days. Given in combination with vinorelbine.
Adenocarcinoma of the pancreas:
Given in combination with Abraxane; see paclitaxel protein-bound particles for injectable suspension monograph.
Clearance decreased in women and the elderly. May be less likely to progress to subsequent cycles; see Precautions and Elderly.
| ||||||||
Treatment of pancreatic cancer and NSCLC:
Reduce dose based on the degree of hematologic toxicity according to the following chart.
| ||||||||||||||||||||
Treatment of breast cancer (combination with paclitaxel):
Reduce dose based on degree of hematologic toxicity according to the following chart.
aSee paclitaxel monograph for additional dose adjustment guidelines. | ||||||||||||||||||||||||||||||||||||
Treatment of ovarian cancer in combination with carboplatin:
Reduce dose based on the degree of hematologic toxicity according to the following charts.
aSee carboplatin monograph for additional dosing guidelines. | ||||||||||||||||||||||||||||||||
Gemcitabine dose modification for myelosuppression in previous cycle in ovarian cancer:
Reduce dose based on myelosuppression occurrence according to the following chart:
aSee carboplatin monograph for additional dosing guidelines. | ||||||||||||
Specific techniques required; see Precautions. Gemzar:
Available in single-use vials containing 200 mg or 1 Gm of gemcitabine. A white to off-white lyophilized powder. Each 200 mg must be reconstituted with 5 mL NS without preservatives (25 mL NS for 1 Gm). Yields 38 mg/mL. Shake to dissolve. Do not use less solution to reconstitute; dissolution will be incomplete. The appropriate dose must be further diluted with NS to concentrations as low as 0.1 mg/mL. 1,500 mg diluted in 250 mL yields 6 mg/mL. 750 mg in 100 mL yields 7.5 mg/mL.
Provided in premixed bags (10 mg/mL) that are ready for infusion and do not require any further preparation before use. Do not dilute before use. Do not remove or add medication. Infugem is a clear, colorless solution. Check for leaks by squeezing inner bag firmly. If leaks are found, discard the bag. Select the gemcitabine premixed bag(s) that allow for a variance of up to 5% of the BSA-calculated dose for all indications. See manufacturer’s prescribing information for charts showing specific size of infusion bags to use based on BSA range.
Specific information not available.
Store unopened vials at CRT. Reconstituted or diluted solutions are stable at CRT for 24 hours. Do not refrigerate in any form; may crystallize. Discard unused portion.
Unopened infusion bags are stable until the expiration date on the package when stored at RT. Do not freeze, as crystallization can occur.
Manufacturer states, “No incompatibilities observed with IV bottles or PVC bags and administration sets.”
Manufacturer states, “Do not remove or add medication.”
Other sources suggest compatibilities for Gemzar dependent on concentration and manufacturer; consult a pharmacist.
A single dose as an infusion equally distributed over 30 minutes.
Infuse all doses of gemcitabine over 30 minutes. If two premixed infusion bags are required to achieve the prescribed dose, infuse the total volume of both bags over 30 minutes.
Do not extend infusion time beyond 60 minutes; will increase toxicity.
A nucleoside metabolic inhibitor with antineoplastic activity. Metabolized intracellularly to two active nucleosides. Cell phase specific, these nucleosides induce internucleosomal DNA fragmentation, primarily killing cells undergoing DNA synthesis (S-phase) and also blocking the progression of cells through the G1/S-phase boundary. Very little is bound to plasma protein. Volume of distribution is increased by infusion length. Half-life is shorter (42 to 94 minutes) with a short infusion (less than 70 minutes), and longer (245 to 638 minutes) with a long infusion (more than 70 minutes). Half-life is slightly longer and rate of clearance is lower in women and in the elderly, resulting in higher concentrations for any given dose. Primarily excreted in urine.
First-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas in patients previously treated with fluorouracil. ■ First-line treatment in combination with cisplatin for the treatment of inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non–small-cell lung cancer. ■ First-line treatment in combination with paclitaxel for treatment of metastatic breast cancer after failure of previous anthracycline chemotherapy unless anthracyclines (e.g., doxorubicin [Adriamycin], idarubicin [Idamycin]) were clinically contraindicated. ■ Treatment in combination with carboplatin for patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.
Treatment of metastatic bladder cancer. ■ Treatment of testicular cancer. ■ Treatment of cancer of the head and neck. ■ Treatment of Hodgkin lymphoma (relapsed) or non-Hodgkin lymphoma (refractory).
Follow guidelines for handling cytotoxic agents. See Appendix A. ■ Administered by or under the direction of the physician specialist. ■ Adequate diagnostic and treatment facilities must be available. ■ For IV use only. May be administered on an outpatient basis. ■ Prolongation of the infusion time beyond 60 minutes and more frequent than weekly dosing have been shown to increase toxicity (e.g., clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia). ■ Myelosuppression (e.g., anemia, neutropenia, and thrombocytopenia) is the dose-limiting toxicity. Occurs with gemcitabine as a single agent, and the risk increases when it is combined with other cytotoxic drugs; see Dose Adjustments. ■ Clearance in women and the elderly is reduced; women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3 or 4 neutropenia and thrombocytopenia. No age or gender dose adjustments recommended. ■ Use with caution in impaired renal or hepatic function. Clear dose recommendations are not available; data from clinical studies insufficient. ■ Hepatotoxicity, including liver failure and death, has been reported. Use in patients with concurrent liver metastases or a history of alcoholism, hepatitis, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency. ■ Hemolytic-uremic syndrome (HUS) and/or renal toxicity, including renal failure leading to death or requiring dialysis, has been reported. Serious cases of thrombotic microangiopathy other than HUS have been reported. ■ Gemcitabine is a potent radiosensitizer. Concurrent use of gemcitabine with radiation therapy (or using 7 or fewer days apart from radiation therapy) may cause severe, life-threatening mucositis, especially esophagitis and pneumonitis. Data suggest that gemcitabine can be administered if given more than 7 days before or after radiation therapy. Radiation recall has been reported in patients who receive gemcitabine after prior radiation. ■ Pulmonary toxicity (e.g., adult respiratory distress syndrome [ARDS], interstitial pneumonitis, pulmonary edema, pulmonary fibrosis) has been reported. Fatalities have occurred. Onset of pulmonary symptoms may occur up to 2 weeks after the last dose of gemcitabine. Discontinue gemcitabine in patients who develop unexplained dyspnea, with or without bronchospasm, or who have any evidence of pulmonary toxicity. ■ Capillary leak syndrome (CLS) and posterior reversible encephalopathy syndrome (PRES) have been reported. ■ Use caution in patients who have had previous cytotoxic chemotherapy or radiation therapy.
Monitor for bone marrow suppression. Obtain a CBC, including differential and platelet count, before each dose; see Dose Adjustments. ■ Obtain baseline renal function (e.g., SCr) and liver function tests (e.g., AST, ALT) and repeat periodically. ■ Monitor serum calcium, magnesium, potassium, and SCr during combination therapy with cisplatin. ■ Monitor vital signs. ■ Monitor respiratory status. ■ Maintain adequate hydration. ■ Nausea and vomiting are frequent and were severe in 15% of patients; prophylactic administration of antiemetics will increase patient comfort. ■ Observe closely for S/S of infection. May cause fever in the absence of infection, or prophylactic antibiotics may be indicated pending results of C/S in a febrile or nonfebrile patient. ■ Monitor for thrombocytopenia (platelet count less than 50,000/mm3). Initiate precautions to prevent excessive bleeding (e.g., inspect IV sites, skin, and mucous membranes; use extreme care during invasive procedures; test urine, emesis, stool, and secretions for occult blood). ■ Consider a diagnosis of HUS if anemia with evidence of microangiopathic hemolysis, elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or evidence of renal failure (elevation of SCr or BUN) develops; discontinue gemcitabine. ■ Monitor for S/S of CLS (sudden edema, rapid drop in blood pressure, shock, hemoconcentration, hypoalbuminemia). ■ Monitor for S/S of PRES (blindness, confusion, headache, hypertension, lethargy, seizure, or other visual or neurologic disturbances). Confirm diagnosis of PRES with MRI. ■ Not a vesicant, but monitor injection site for inflammation and/or extravasation.
Effective birth control is recommended for females of reproductive potential and males with female partners of reproductive potential during and for 6 months (females) and for 3 months (males) after the last dose of gemcitabine. ■ May impair fertility in males of reproductive potential. ■ Report any unusual or unexpected symptoms or side effects (e.g., shortness of breath, cough, wheezing, blood in stool or urine, change in color or volume of urine, S/S of infection, jaundice, pain/tenderness in the right upper abdominal quadrant, unusual bruising or bleeding) as soon as possible. ■ See Appendix D, p. 1311.
Avoid pregnancy. May cause fetal harm. ■ Discontinue breast-feeding during treatment and for at least 1 week after the last dose. ■ Safety and effectiveness for use in pediatric patients not established.
Clearance reduced in the elderly; hematologic toxicity requiring reduction, delay, or omission of subsequent doses is higher than in younger adults; however, incidence of nonhematologic toxicity is similar. Elderly men and women are more likely to experience Grade 3 or 4 thrombocytopenia. Elderly women are also more likely to experience Grade 3 or 4 neutropenia. Usual dose adjustments based on toxicity are considered appropriate. Age-related impaired renal function may further reduce clearance and increase toxicity.
Interaction of gemcitabine with other drugs has not been adequately studied. ■ Do not administer live virus vaccines to patients receiving antineoplastic agents.
The most common side effects are anemia, dyspnea, fever, hematuria, increased alkaline phosphatase, AST and ALT, nausea, neutropenia, peripheral edema, proteinuria, rash, thrombocytopenia, and vomiting. Less frequently reported side effects include alopecia, anorexia, arthralgia, bone marrow toxicity (e.g., anemia, leukopenia, neutropenia, thrombocytopenia), bone pain, bronchospasm, cerebrovascular accident, constipation, diarrhea, edema, elevated lab tests (e.g., BUN, creatinine, hematuria, proteinuria), fatigue, febrile neutropenia, flu syndrome (e.g., anorexia, chills, cough, headache, myalgia, weakness), hemorrhage, hepatotoxicity, hypertension, increased liver function tests (e.g., ALT, AST, GGT, alkaline phosphatase, and bilirubin), infection, injection site reaction, myalgia, neuropathy (motor and sensory), pain, paresthesias, pruritus, pulmonary toxicity (including respiratory failure), radiation recall reactions, somnolence, and stomatitis. Anaphylaxis and hemolytic-uremic syndrome have been reported.
Adult respiratory distress syndrome (ARDS), arrhythmias, capillary leak syndrome, cellulitis, congestive heart failure, gangrene, hepatic failure, hepatic veno-occlusive disease, interstitial pneumonitis, myocardial infarction, peripheral vasculitis, posterior reversible encephalopathy syndrome (PRES), pulmonary edema, pulmonary eosinophilia, pulmonary fibrosis, pseudocellulitis, severe skin reactions (including desquamation and bullous skin eruptions), supraventricular arrhythmias, and thrombotic microangiopathy (TMA).
Keep physician informed of all side effects. Symptomatic and supportive treatment is indicated. Permanently discontinue gemcitabine if any of the following occur: unexplained dyspnea or other evidence of severe pulmonary toxicity, severe hepatic toxicity, hemolytic uremic syndrome or severe renal impairment, capillary leak syndrome, or posterior reversible encephalopathy syndrome (PRES). Reduce dose or withhold gemcitabine until myelosuppression improves to specific criteria; see Dose Adjustments. Anemia may require RBC transfusions. Other whole blood products (e.g., platelets, leukocytes) and/or blood modifiers (e.g., darbepoetin alfa, epoetin alfa, filgrastim, pegfilgrastim, sargramostim) may be indicated to treat bone marrow toxicity. Most side effects are reversible with dose reduction or temporary withholding of gemcitabine. No known antidote for overdose. If hemolytic-uremic syndrome occurs, discontinue gemcitabine; renal failure may not be reversible even with discontinuation of therapy, and dialysis may be required. Treat hypersensitivity reactions as indicated; may require epinephrine, airway management, oxygen, IV fluids, antihistamines (e.g., diphenhydramine), corticosteroids (e.g., hydrocortisone sodium succinate), and pressor amines (e.g., dopamine).