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Pronunciation
(jem SITE a been)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of metastatic breast cancer; inoperable locally-advanced or metastatic nonsmall cell lung cancer (NSCLC); locally advanced or metastatic pancreatic cancer; advanced, relapsed ovarian cancer
Use: Unlabeled/Investigational
Treatment of biliary tract cancers (advanced), bladder cancer, cervical cancer (recurrent or persistent), Ewing's sarcoma (refractory), head and neck cancer (nasopharyngeal), Hodgkin's lymphoma (relapsed), non-Hodgkin's lymphomas (refractory), malignant pleural mesothelioma, osteosarcoma (refractory), renal cell cancer (metastatic), small cell lung cancer (refractory or relapsed), soft tissue sarcoma (advanced), testicular cancer (refractory germ cell tumors), thymic malignancies, uterine sarcoma, and unknown-primary adenocarcinoma
Pregnancy Risk Factor
D
Pregnancy Considerations
Embryotoxicity and fetal malformations (cleft palate, incomplete ossification, fused pulmonary artery, absence of gallbladder) have been reported in animal studies. There are no adequate and well-controlled studies in pregnant women. If patient becomes pregnant, she should be informed of risks.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in nursing the infant, breast-feeding is not recommended.
Contraindications
Hypersensitivity to gemcitabine or any component of the formulation
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: May cause bone marrow suppression (leukopenia, thrombocytopenia, and anemia); myelosuppression is usually the dose-limiting toxicity. Monitor blood counts.
• Fever: May cause fever in the absence of clinical infection.
• Hemolytic uremic syndrome: Hemolytic uremic syndrome has been reported; monitor for evidence of microangiopathic hemolysis (elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or renal failure).
• Hepatotoxicity: Serious hepatotoxicity (including liver failure and death) has been reported when used in combination with other chemotherapy; use with caution in patients with hepatic impairment (history of cirrhosis, hepatitis, or alcoholism) or in patients with hepatic metastases; may lead to exacerbation of hepatic impairment. Dose adjustments may be recommended with elevated bilirubin.
• Pulmonary toxicity: Pulmonary toxicity has been observed; discontinue if severe and institute supportive measures.
Disease-related concerns:
• Renal impairment: Use with caution in patients with pre-existing renal impairment.
Special populations:
• Elderly: Use with caution in the elderly; clearance is affected by age.
• Radiation therapy recipients: Use with caution with concurrent radiation therapy; radiation toxicity has been reported with concurrent and nonconcurrent administration; may have radiosensitizing activity when gemcitabine and radiation therapy are given ≤7 days apart; optimum regimen for combination therapy has not been determined for all tumor types.
Other warnings/precautions:
• Administration: Prolongation of the infusion time >60 minutes and more frequent than weekly dosing have been shown to increase toxicity.
Adverse Reactions
Frequency of adverse reactions reported for single-agent use of gemcitabine only.
>10%:
Cardiovascular: Peripheral edema (20%), edema (13%)
Central nervous system: Fever (38% to 41%), somnolence (11%)
Dermatologic: Rash (28% to 30%), alopecia (15% to 16%), pruritus (13%)
Gastrointestinal: Nausea/vomiting (69% to 71%; grade 3: 10% to 13%; grade 4: 1% to 2%), diarrhea (19% to 30%), stomatitis (10% to 11%)
Hematologic: Anemia (68% to 73%; grade 4: 1% to 2%), leukopenia (62% to 64%; grade 4: ≤1%), neutropenia (61% to 63%; grade 4: 6% to 7%), thrombocytopenia (24% to 36%; grade 4: ≤1%), hemorrhage (4% to 17%; grades 3: ≤2%; grade 4: <1%); myelosuppression is the dose-limiting toxicity
Hepatic: AST increased (67% to 78%; grade 3: 6% to 12%; grade 4: 2% to 5%), alkaline phosphatase increased (55% to 77%; grade 3: 7% to 16%; grade 4: 2% to 4%), ALT increased (68% to 72%; grade 3: 8% to 10%; grade 4: 1% to 2%), bilirubin increased (13% to 26%; grade 3: 2% to 6%; grade 4: ≤2%)
Renal: (32% to 45%; grades 3/4: <1%), hematuria (23% to 35%; grades 3/4: <1%), BUN increased (15% to 16%)
Respiratory: Dyspnea (10% to 23%)
Miscellaneous: Flu-like syndrome (19%), infection (10% to 16%; grade 3: 1% to 2%; grade 4: <1%)
1% to 10%:
Local: Injection site reactions (4%)
Neuromuscular & skeletal: Paresthesia (10%)
Renal: Creatinine increased (6% to 8%)
Respiratory: Bronchospasm (<2%)
<1%, postmarketing, and/or case reports (reported with single-agent use or with combination therapy): Acute/adult respiratory distress syndrome, anaphylactoid reaction, anorexia, arrhythmias, arthralgia, bullous skin eruptions, cellulitis, cerebrovascular accident, CHF, chills, constipation, cough, desquamation, diaphoresis, fulminant hepatic failure, gangrene, GGT increased, headache, hemolytic uremic syndrome (HUS), hepatotoxicity (rare), hyperglycemia, hyper-/hypotension, hypermagnesemia, hypocalcemia, insomnia, interstitial pneumonitis, liver failure, malaise, MI, myalgia, neuropathy, peripheral vasculitis, petechiae, pulmonary edema, pulmonary fibrosis, radiation recall, renal failure, respiratory failure, reversible posterior leukoencephalopathy syndrome (RPLS), rhinitis, sepsis, supraventricular arrhythmia, thrombotic thrombocytopenic purpura, veno-occlusive liver disease, weakness
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bleomycin: Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Risk D: Consider therapy modification
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Fluorouracil: Gemcitabine may increase the serum concentration of Fluorouracil. Risk C: Monitor therapy
Fluorouracil (Systemic): Gemcitabine may increase the serum concentration of Fluorouracil (Systemic). Risk C: Monitor therapy
Fluorouracil (Topical): Gemcitabine may increase the serum concentration of Fluorouracil (Topical). Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Storage
Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Reconstituted vials are stable for up to 35 days and infusion solutions diluted in 0.9% sodium chloride are stable up to 7 days at 23°C when protected from light; however, the manufacturers recommend use within 24 hours for both reconstituted vials and infusion solutions. Do not refrigerate.
Reconstitution
Use appropriate precautions for handling and disposal. Reconstitute with preservative free 0.9% NaCl; add 5 mL to the 200 mg vial, add 25 mL to the 1000 mg vial, or add 50 mL to the 2000 mg vial, resulting in a reconstituted concentration of 38 mg/mL (solutions must be reconstituted to ≤40 mg/mL to completely dissolve). Further dilute (for infusion) in 50-500 mL 0.9% sodium chloride injection; to concentrations as low as 0.1 mg/mL.
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Amifostine, amikacin, aminophylline, ampicillin, ampicillin/sulbactam, anidulafungin, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chlorpromazine, cimetidine, ciprofloxacin, cisplatin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dactinomycin, daunorubicin HCl, dexamethasone sodium phosphate, dexrazoxane, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxycycline, droperidol, enalaprilat, etoposide, etoposide phosphate, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, gentamicin, granisetron, haloperidol lactate, heparin, hydrocortisone sodium succinate, hydromorphone, hydroxyzine HCl, idarubicin, ifosfamide, leucovorin calcium, linezolid, lorazepam, mannitol, meperidine, mesna, metoclopramide, metronidazole, mitoxantrone, morphine, nalbuphine, ofloxacin, ondansetron, oxaliplatin, paclitaxel, palonosetron, potassium chloride, promethazine, ranitidine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin/clavulanate, tobramycin, topotecan, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Acyclovir, amphotericin B, cefotaxime, furosemide, ganciclovir, imipenem/cilastatin, irinotecan, methotrexate, methylprednisolone sodium succinate, mitomycin, pemetrexed, piperacillin, piperacillin/tazobactam, prochlorperazine edisylate.
Mechanism of Action
A pyrimidine antimetabolite that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase, specific for the S-phase of the cycle. Gemcitabine is phosphorylated intracellularly by deoxycytidine kinase to gemcitabine monophosphate, which is further phosphorylated to active metabolites gemcitabine diphosphate and gemcitabine triphosphate. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase; gemcitabine triphosphate incorporates into DNA and inhibits DNA polymerase.
Pharmacodynamics/Kinetics
Distribution: Infusions <70 minutes: 50 L/m2; Long infusion times (70-285 minutes): 370 L/m2
Protein binding: Low
Metabolism: Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites
Half-life elimination:
Gemcitabine: Infusion time ≤70 minutes: 42-94 minutes; infusion time 3-4 hours: 4-10.5 hours
Metabolite (gemcitabine triphosphate), terminal phase: 1.7-19.4 hours
Time to peak, plasma: 30 minutes after completion of infusion
Excretion: Urine (92% to 98%; primarily as inactive uracil metabolite); feces (<1%)
Dosage
Details concerning dosing in combination regimens should also be consulted. Note: Prolongation of the infusion time >60 minutes and administration more frequently than once weekly have been shown to increase toxicity. I.V.:
Children (refer to specific references for ages of populations studied):
Germ cell tumor, refractory (unlabeled use): 1000 mg/m2/dose days 1, 8, and 15 every 4 weeks (in combination with paclitaxel) (Hinton, 2002)
Hodgkin's lymphoma, relapsed (unlabeled use): 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine) (Cole; 2009) or 800 mg/m2 days 1 and 4; repeat cycle every 21 days (in combination with ifosfamide, mesna, vinorelbine, and prednisolone) (Santoro, 2007)
Sarcomas (unlabeled use):
Ewing's sarcoma, refractory: 675 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008)
Osteosarcoma, refractory: 675 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008) or 1000 mg/m2 weekly for 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks (Merimsky, 2000)
Adults:
Pancreatic cancer, locally advanced or metastatic: Initial: 1000 mg/m2 weekly for up to 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks
Dose adjustment: Patients who complete an entire cycle of therapy may have the dose in subsequent cycles increased by 25% as long as the absolute granulocyte count (AGC) nadir is >1500 x 106/L, platelet nadir is >100,000 x 106/L, and nonhematologic toxicity is less than WHO Grade 1. If the increased dose is tolerated (with the same parameters) the dose in subsequent cycles may again be increased by 20%.
Pancreatic cancer, advanced (unlabeled dosing/combinations): 1000 mg/m2 weekly for up to 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks (in combination with erlotinib) (Moore, 2007) or 1000 mg/m2 days 1, 8, and 15 every 4 weeks (in combination with capecitabine) (Cunningham, 2009) or 1000 mg/m2 days 1 and 15 every 4 weeks (in combination with cisplatin) (Heinemann, 2006) or 1000 mg/m2 every 2 weeks (in combination with oxaliplatin) (Louvet, 2005)
Nonsmall cell lung cancer (in combination with cisplatin): 1000 mg/m2 days 1, 8, and 15; repeat cycle every 28 days or 1250 mg/m2 days 1 and 8; repeat cycle every 21 days
Breast cancer, metastatic: 1250 mg/m2 days 1 and 8; repeat cycle every 21 days in combination with paclitaxel or (unlabeled dosing) as a single agent: 800 mg/m2 days 1, 8, and 15 of a 28-day treatment cycle (Carmichael, 1995)
Ovarian cancer, advanced: 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with carboplatin)
Biliary tract cancer, advanced (unlabeled use): 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Valle, 2010) or 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with capecitabine) (Knox, 2005) or 1000 mg/m2 over 100 minutes every 2 weeks (in combination with oxaliplatin) (Andre, 2004)
Bladder cancer (unlabeled use):
I.V.: 1000 mg/m2 once weekly for 3 weeks; repeat cycle every 4 weeks (in combination with cisplatin) (von der Maase, 2000)
Intravesicular instillation: 2000 mg (in 100 mL NS; retain for 1 hour) twice weekly for 3 weeks; repeat cycle every 4 weeks for at least 2 cycles (Dalbagni, 2006)
Cervical cancer, recurrent or persistent (unlabeled use): 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Monk, 2009) or 1250 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Burnett, 2000) or 800 mg/m2 days 1, 8, and 15; repeat cycle every 28 days (as a single-agent) (Schilder, 2005)
Head and neck cancer, nasopharyngeal (unlabeled use): 1000 mg/m2 days 1, 8, and 15 every 4 weeks (Zhang, 2008)
Hodgkin's lymphoma, relapsed (unlabeled use): 1000 mg/m2 (800 mg/m2 for post-transplant patients) days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine and doxorubicin liposomal) (Bartlett, 2007) or 800 mg/m2 days 1 and 4; repeat cycle every 21 days (in combination with ifosfamide, mesna, vinorelbine, and prednisolone) (Santoro, 2007)
Malignant pleural mesothelioma (unlabeled use; in combination with cisplatin): 1000 mg/m2/dose days 1, 8 and 15 every 4 weeks (Nowak, 2002) or 1250 mg/m2/dose days 1 and 8 every 3 weeks (van Haarst, 2002)
Non-Hodgkin's lymphoma, refractory (unlabeled use): 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with cisplatin and dexamethasone) (Crump, 2004) or 1000 mg/m2 every 15-21days (in combination with oxaliplatin and rituximab) (Lopez, 2008)
Sarcoma (unlabeled uses):
Ewing's sarcoma, refractory: 675 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008)
Osteosarcoma, refractory: 675 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008) or 1000 mg/m2 weekly for 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks (Merimsky, 2000)
Soft tissue sarcoma, advanced: 800 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine) (Dileo, 2007) or 675 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Leu, 2004) or 900 mg/m2 days 1 and 8; repeat cycle every 21 days (fixed dose rate infusion; in combination with docetaxel) (Maki, 2007)
Small cell lung cancer, refractory or relapsed (unlabeled use): 1000-1250 mg/m2 days 1, 8, and 15 every 4 weeks (as a single agent) (Masters, 2003)
Testicular cancer, refractory germ cell (unlabeled use): 1000 mg/m2 days 1 and 8 every 3 weeks (in combination with oxaliplatin) (Kohllmannsberger, 2004; Pectasides, 2004) or 1250 mg/m2 days 1 and 8 every 3 weeks (in combination with oxaliplatin) (De Giorgi, 2006) or 1000 mg/m2/dose days 1, 8, and 15 every 4 weeks (in combination with paclitaxel) (Hinton, 2002)
Unknown-primary, adenocarcinoma (unlabeled use): 1250 mg/m2 days 1 and 8 every 3 weeks (in combination with cisplatin) (Culine, 2003) or 1000 mg/m2 days 1 and 8 every 3 weeks (in combination with docetaxel) (Pouessel, 2004)
Uterine cancer (unlabeled use): 900 mg/m2 days 1 and 8 every 3 weeks (in combination with docetaxel) (Hensley, 2008) or 1000 mg/m2 days 1, 8, and 15 every 4 weeks (Look, 2004)
Dosing adjustment for toxicity:
Pancreatic cancer: Hematologic toxicity:
AGC ≥1000 x 106/L and platelet count ≥100,000 x 106/L: Administer 100% of full dose
AGC 500-999 x 106/L or platelet count 50,000-90,000 x 106/L: Administer 75% of full dose
AGC <500 x 106/L or platelet count <50,000 x 106/L: Hold dose
Nonsmall cell lung cancer:
Hematologic toxicity: Refer to guidelines for pancreatic cancer. Cisplatin dosage may also need adjusted.
Severe (grades 3 or 4) nonhematologic toxicity (except alopecia, nausea, and vomiting): Hold or decrease dose by 50%.
Breast cancer:
Hematologic toxicity: Adjustments based on granulocyte and platelet counts on day 8:
AGC ≥1200 x 106/L and platelet count >75,000 x 106/L: Administer 100% of full dose
AGC 1000-1199 x 106/L or platelet count 50,000-75,000 x 106/L: Administer 75% of full dose
AGC 700-999 x 106/L and platelet count ≥50,000 x 106/L: Administer 50% of full dose
AGC <700 x 106/L or platelet count <50,000 x 106/L: Hold dose
Severe (grades 3 or 4) nonhematologic toxicity (except alopecia, nausea, and vomiting): Hold or decrease dose by 50%. Paclitaxel dose may also need adjusted.
Ovarian cancer:
Hematologic toxicity: Adjustments based on granulocyte and platelet counts on day 8:
AGC ≥1500 x 106/L and platelet count ≥100,000 x 106/L: Administer 100% of full dose
AGC 1000-1499 x 106/L and/or platelet count 75,000-99,999 x 106/L: Administer 50% of full dose
AGC <1000 x 106/L and/or platelet count <75,000 x 106/L: Hold dose
Severe (grades 3 or 4) nonhematologic toxicity (except nausea and vomiting): Hold or decrease dose by 50%. Carboplatin dose may also need adjusted.
Dose adjustment for subsequent cycles:
AGC < 500 x 106/L for >5 days, AGC <100 x 106/L for >3 days, febrile neutropenia, platelet count <25,000 x 106/L, cycle delay >1 week due to toxicity: Reduce gemcitabine to 800 mg/m2 on days 1 and 8.
For recurrence of any of the above toxicities after initial dose reduction: Administer gemcitabine 800 mg/m2 on day 1 only for the subsequent cycle
Dosing adjustment in renal impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with caution in patients with pre-existing renal dysfunction. Discontinue if severe renal toxicity or hemolytic uremic syndrome (HUS) occur during gemcitabine treatment.
Mild-to-severe renal impairment: No adjustment required (Janus, 2010; Li, 2007)
ESRD (on hemodialysis): Hemodialysis should begin 6-12 hours after gemcitabine infusion (Janus 2010; Li, 2007)
Dosing adjustment in hepatic impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with caution. Discontinue if severe hepatotoxicity occurs during treatment with gemcitabine. The following guidelines have been used by some clinicians:
Transaminases elevated (with normal bilirubin): No adjustment required (Venook, 2000)
Serum bilirubin >1.6 mg/dL: Use initial dose of 800 mg/m2; may escalate if tolerated (Ecklund, 2005; Floyd, 2006; Venook, 2000)
Dosage: Combination Regimens
Biliary adenocarcinoma:
Gemcitabine-Capecitabine (Biliary Cancer)
Gemcitabine-Cisplatin (Biliary Cancer)
GEMOX (Biliary Cancer)
Bladder cancer:
Gemcitabine-Carboplatin (Bladder Cancer)
Gemcitabine-Cisplatin (Bladder Cancer)
Paclitaxel-Carboplatin-Gemcitabine
Paclitaxel-Gemcitabine
Breast cancer: Gemcitabine-Paclitaxel (Breast Cancer)
Cervical cancer: Cisplatin-Gemcitabine (Cervical Cancer)
Lung cancer (nonsmall cell):
Bevacizumab-Cisplatin-Gemcitabine
Gemcitabine-Carboplatin (NSCLC)
Gemcitabine-Cisplatin (NSCLC)
Gemcitabine-Vinorelbine (NSCLC)
Lymphoma, Hodgkin's disease: Gemcitabine-Vinorelbine-Doxorubicin (Liposomal)
Lymphoma, non-Hodgkin's: Gemcitabine-Oxaliplatin-Rituximab (NHL)
Malignant pleural mesothelioma: Gemcitabine-Cisplatin (Mesothelioma)
Osteosarcoma: Gemcitabine-Docetaxel (Sarcoma)
Ovarian cancer:
Gemcitabine-Carboplatin (Ovarian Cancer)
Gemcitabine-Paclitaxel (Ovarian Cancer)
Pancreatic cancer:
Gemcitabine-Capecitabine (Pancreatic Cancer)
Gemcitabine-Cisplatin (Pancreatic Cancer)
Gemcitabine-Erlotinib (Pancreatic Cancer)
Gemcitabine-Oxaliplatin (Pancreatic Cancer)
Renal cell cancer:
Gemcitabine-Capecitabine (RCC)
Gemcitabine-Fluorouracil (RCC)
Soft tissue sarcoma:
Gemcitabine-Docetaxel (Sarcoma)
Gemcitabine-Vinorelbine (Sarcoma)
Testicular cancer: GEMOX (Testicular Cancer)
Unknown primary, adenocarcinoma:
Gemcitabine-Cisplatin (Unknown Primary)
Gemcitabine-Docetaxel (Unknown Primary)
Paclitaxel-Carboplatin-Gemcitabine (Unknown Primary)
Administration: I.V.
Infuse over 30 minutes. Note: Prolongation of the infusion time >60 minutes has been shown to increase toxicity (some unlabeled protocols may include infusion times >30 minutes). Gemcitabine is being investigated in clinical trials for fixed dose rate (FDR) infusion administration at doses from 1000-2200 mg/m2 at a rate of 10 mg/m2/minute. Prolonged infusion times increase the accumulation of the active metabolite, gemcitabine triphosphate. Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity.
Administration: Other
For intravesicular (bladder) instillation, gemcitabine was diluted in 50-100 mL normal saline; patients were instructed to retain in the bladder for 1 hour (Addeo, 2010; Dalbaghi, 2006)
Administration: I.V. Detail
pH: 2.7-3.3
Monitoring Parameters
CBC with differential and platelet count (prior to each dose); hepatic and renal function (prior to initiation of therapy and periodically, thereafter); monitor electrolytes, including potassium, magnesium, and calcium (when in combination therapy with cisplatin)
Patient Education
You will be monitored during infusion. Report immediately any pain, burning, or swelling at infusion site; sudden chest pain or palpitations; difficulty breathing or swallowing; or chills. Between infusions, maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. You may be more susceptible to infection. You may experience new fatigue, lethargy, somnolence, nausea, vomiting, loss of hair (reversible), or mouth sores. Report extreme fatigue; severe GI upset, constipation, or diarrhea; unusual bleeding or bruising; fever, chills, or sore throat; vaginal discharge; signs of fluid retention (swelling of extremities, respiratory difficulty, unusual weight gain); yellowing of skin or eyes; change in color of urine or stool; or muscle or skeletal pain or weakness.
Geriatric Considerations
Clearance is affected by age. There is no evidence; however, that unusual dose adjustment is necessary in patients older than 65 years of age. In general, adverse reaction rates were similar to patients older and younger than 65 years. Grade 3/4 thrombocytopenia was more common in the elderly. Older women were more likely to experience grade 3/4 neutropenia and thrombocytopenia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Leukopenia is common; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Use caution in presence of renal or hepatic impairment. Assess CBC with differential and platelet count prior to each dose. Monitor hepatic and renal function. Monitor for fever, CNS changes, rash, gastrointestinal upset, myelosuppression, anemia, dyspnea, and infection prior to each treatment and on a regular basis.
Oncology: Emetic Potential
Low (10% to 30%)
Oncology: Vesicant
May be an irritant
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 200 mg, 1 g, 2 g
Gemzar®: 200 mg, 1 g
Pricing: U.S. (www.drugstore.com)
Solution (reconstituted) (Gemzar)
1 g (1): $850.02
200 mg (1): $170.43
References
Addeo R, Caraglia M, Bellini S, et al, “Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance,” J Clin Oncol, 2010, 28(4):543-8.
Albain KS, Nag SM, Calderillo-Ruiz G, et al, "Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment," J Clin Oncol, 2008, 26(24):3950-7.
Andre T, Tournigand C, Rosmorduc O, et al, “Gemcitabine Combined With Oxaliplatin (GEMOX) in Advanced Biliary Tract Adenocarcinoma: A GERCOR Study,” Ann Oncol, 2004, 15(9):1339-43.
Bartlett NL, Niedzwiecki D, Johnson JL, et al, "Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin (GVD), a Salvage Regimen in Relapsed Hodgkin's Lymphoma: CALGB 59804," Ann Oncol, 2007, 18(6):1071-9.
Bredenfeld H, Franklin J, Nogova L, et al, “Severe Pulmonary Toxicity in Patients With Advanced-Stage Hodgkin's Disease Treated With a Modified Bleomycin, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone, and Gemcitabine (BEACOPP) Regimen is Probably Related to the Combination of Gemcitabine and Bleomycin: A Report of the German Hodgkin's Lymphoma Study Group,” J Clin Oncol, 2004, 22(12):2424-9.
Burnett AF, Roman LD, Garcia AA, "A Phase II Study of Gemcitabine and Cisplatin in Patients With Advanced, Persistent, or Recurrent Squamous Cell Carcinoma of the Cervix," Gynecol Oncol, 2000, 76(1):63-6.
Carmichael J, Possinger K, Phillip P, et al, “Advanced Breast Cancer: A Phase II Trial With Gemcitabine,” J Clin Oncol, 1995, 13(11):2731-6.
Cole PD, Schwartz CL, Drachtman RA, et al, "Phase II Study of Weekly Gemcitabine and Vinorelbine for Children With Recurrent or Refractory Hodgkin's Disease: A Children's Oncology Group Report," J Clin Oncol, 2009, 27(9):1456-61.
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Last full review/revision May 2011
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