(jem SITE a been)
Breast cancer: First-line treatment of metastatic breast cancer (in combination with paclitaxel) after failure of adjuvant chemotherapy which contained an anthracycline (unless contraindicated)
Non-small cell lung cancer (NSCLC): First-line treatment of inoperable, locally-advanced (stage IIIA or IIIB) or metastatic (stage IV) NSCLC (in combination with cisplatin)
Ovarian cancer: Treatment of advanced ovarian cancer (in combination with carboplatin) that has relapsed at least 6 months following completion of platinum-based chemotherapy
Pancreatic cancer: First-line treatment of locally-advanced (nonresectable stage II or III) or metastatic (stage IV) pancreatic adenocarcinoma
Hypersensitivity to gemcitabine or any component of the formulation
Note: Prolongation of the infusion duration >60 minutes and administration more frequently than once weekly have been shown to increase toxicity.
Breast cancer, metastatic: IV: 1250 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with paclitaxel) or (off-label dosing; as a single agent) 800 mg/m2 over 30 minutes days 1, 8, and 15 of a 28-day treatment cycle (Carmichael, 1995)
Non-small cell lung cancer, locally advanced or metastatic: IV: 1000 mg/m2 over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with cisplatin) or 1250 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) or (off-label dosing/combination) 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) for up to 4 cycles (Gr ƒ ¸nberg, 2009) or (off-label combination) 1000 mg/m2 over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with carboplatin) for up to 4 cycles (Danson, 2003) or (off-label combination) 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) for 8 cycles (Pujol, 2005) or (off-label combination) 1000 mg/m2 days 1, 8, and 15; repeat cycle every 28 days (in combination with vinorelbine) for 6 cycles (Greco, 2007)
Ovarian cancer, advanced: IV: 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) or (off-label dosing; as a single agent) 1000 mg/m2 over 30-60 minutes days 1 and 8; repeat cycle every 21 days (Mutch, 2007)
Pancreatic cancer, locally advanced or metastatic: IV: Initial: 1000 mg/m2 over 30 minutes once weekly for 7 weeks followed by 1 week rest; then once weekly for 3 weeks out of every 4 weeks or (off-label combinations) 1000 mg/m2 over 30 minutes 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 over 30 minutes days 1, 8, and 15 every 28 days (in combination with capecitabine) (Cunningham, 2009) or 1000 mg/m2 over 30 minutes days 1 and 15 every 28 days (in combination with cisplatin) (Heinemann, 2006) or 1000 mg/m2 infused at 10 mg/m2/minute every 14 days (in combination with oxaliplatin) (Louvet, 2005) or 1000 mg/m2 days 1, 8, and 15 every 28 days (in combination with paclitaxel [protein bound]) (Von Hoff, 2013)
Bladder cancer (off-label use):
Advanced or metastatic: IV: 1000 mg/m2 over 30-60 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with cisplatin) (von der Maase, 2000) or 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) until disease progression or unacceptable toxicity (De Santis, 2012)
Transitional cell carcinoma: 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 (off-label use): IV: 1000 mg/m2 days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Monk, 2009) or 1250 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Burnett, 2000) or 800 mg/m2 over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (as a single-agent) (Schilder, 2005) or 800 mg/m2 days 1 and 8; repeat cycle every 28 days (in combination with cisplatin) (Brewer, 2006)
Head and neck cancer, nasopharyngeal (off-label use): IV: 1000 mg/m2 over 30 minutes days 1, 8, and 15 every 28 days (Zhang, 2008) or 1000 mg/m2 over 30 minutes days 1 and 8 every 21 days (in combination with vinorelbine) (Chen, 2012)
Hepatobiliary cancer, advanced (off-label use): IV: 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Valle, 2010) or 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with capecitabine) (Knox, 2005) or 1000 mg/m2 infused at 10 mg/m2/minute every 2 weeks (in combination with oxaliplatin) (Andre, 2004)
Hodgkin lymphoma, relapsed (off-label use): IV: 1000 mg/m2 (800 mg/m2 for post-transplant patients) over 30 minutes 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 (off-label use; in combination with cisplatin): IV: 1000 mg/m2 over 30 minutes days 1, 8 and 15 every 28 days for up to 6 cycles (Nowak, 2002) or 1250 mg/m2 over 30 minutes days 1 and 8 every 21 days for up to 6 cycles (van Haarst, 2002)
Non-Hodgkin lymphoma, refractory (off-label use): IV: 1000 mg/m2 over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin and dexamethasone) (Crump, 2004) or 1000 mg/m2 every 15-21 days (in combination with oxaliplatin and rituximab) (Lopez, 2008)
Sarcoma (off-label uses): IV:
Ewing 's sarcoma, refractory: 675 mg/m2 over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008)
Osteosarcoma, refractory: 675 mg/m2 over 90 minutes 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 over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine) (Dileo, 2007) or 675 mg/m2 over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Leu, 2004) or 900 mg/m2 over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Maki, 2007)
Small cell lung cancer, refractory or relapsed (off-label use): IV: 1000-1250 mg/m2 over 30 minutes days 1, 8, and 15 every 28 days (as a single agent) (Masters, 2003)
Testicular cancer, refractory germ cell (off-label use): IV: 1000-1250 mg/m2 over 30 minutes days 1 and 8 every 21 days (in combination with oxaliplatin) (DeGiorgi, 2006; Kohllmannsberger, 2004; Pectasides, 2004) or 1000 mg/m2 over 30 minutes days 1, 8, and 15 every 28 days for up to 6 cycles (in combination with paclitaxel) (Hinton, 2002) or 800 mg/m2 over 30 minutes days 1 and 8 every 21 days (in combination with oxaliplatin and paclitaxel) (Bokemeyer, 2008)
Unknown-primary, adenocarcinoma (off-label use): IV: 1250 mg/m2 days 1 and 8 every 21 days (in combination with cisplatin) (Culine, 2003) or 1000 mg/m2 over 30 minutes days 1 and 8 every 21 days for up to 6 cycles (in combination with docetaxel) (Pouessel, 2004)
Uterine cancer (off-label use): IV: 900 mg/m2 over 90 minutes days 1 and 8 every 21 days (in combination with docetaxel) (Hensley, 2008) or 1000 mg/m2 over 30 minutes days 1, 8, and 15 every 28 days (Look, 2004)
Refer to adult dosing.
Note: Prolongation of the infusion duration >60 minutes and administration more frequently than once weekly have been shown to increase toxicity. Refer to specific references for ages of populations studied:
Germ cell tumor, refractory (off-label use): IV: 1000 mg/m2 over 30 minutes days 1, 8, and 15 every 28 days (in combination with paclitaxel) for up to 6 cycles (Hinton, 2002)
Hodgkin lymphoma, relapsed (off-label use): IV: 1000 mg/m2 over 100 minutes 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 (off-label use): IV:
Ewing 's sarcoma, refractory: 675 mg/m2 over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid, 2008)
Osteosarcoma, refractory: 675 mg/m2 over 90 minutes 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)
There are no dosage adjustments provided in the manufacturer 's labeling; 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 dosage adjustment necessary (Janus, 2010; Li, 2007).
ESRD (on hemodialysis): Hemodialysis should begin 6-12 hours after gemcitabine infusion (Janus 2010; Li, 2007).
There are no dosage adjustments provided in the manufacturer 's labeling; use with caution. Discontinue if severe hepatotoxicity occurs during gemcitabine treatment. The following adjustments have been reported:
Transaminases elevated (with normal bilirubin): No dosage adjustment necessary (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).
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Reconstitute lyophilized powder with preservative free NS; 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). Gemcitabine is also supplied as a concentrated solution for injection in different concentrations (40 mg/mL [Canada only] and 38 mg/mL); verify product concentration prior to preparation for administration.
Further dilute reconstituted lyophilized powder or concentrated solution for injection in NS for infusion; to concentrations as low as 0.1 mg/mL.
Infuse over 30 minutes; for off-label uses, infusion times may vary (refer to specific references). Note: Prolongation of the infusion time >60 minutes has been shown to increase toxicity. Gemcitabine has been administered at a fixed-dose rate (FDR) infusion rate of 10 mg/m2/minute to optimize the pharmacokinetics (off-label); prolonged infusion times increase the intracellular accumulation of the active metabolite, gemcitabine triphosphate (Ko, 2006; Tempero, 2003). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ko, 2006; Poplin, 2009).
For intravesicular (bladder) instillation (off-label route), gemcitabine was diluted in 50 to 100 mL normal saline; patients were instructed to retain in the bladder for 1 hour (Addeo, 2010; Dalbaghi, 2006)
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Lyophilized powder: 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 24 hours at room temperature. Do not refrigerate (may form crystals).
Solution for injection: Store intact vials refrigerated at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze.
Solutions diluted for infusion in NS are stable for 24 hours at room temperature. Do not refrigerate.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 200 mg/5.26 mL (5.26 mL); 1 g/26.3 mL (26.3 mL); 2 g/52.6 mL (52.6 mL)
Solution, Intravenous [preservative free]:
Generic: 200 mg/5.26 mL (5.26 mL); 1 g/26.3 mL (26.3 mL); 2 g/52.6 mL (52.6 mL)
Solution Reconstituted, Intravenous:
Gemzar: 200 mg (1 ea); 1 g (1 ea)
Generic: 200 mg (1 ea); 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 200 mg (1 ea); 1 g (1 ea)
Stable in D5W, NS.
Y-site administration: Incompatible with acyclovir, amphotericin B, cefotaxime, furosemide, ganciclovir, imipenem/cilastatin, irinotecan, methotrexate, methylprednisolone sodium succinate, mitomycin, pemetrexed, piperacillin, piperacillin/tazobactam, prochlorperazine edisylate.
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bleomycin: Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Fluorouracil (Systemic): Gemcitabine may increase the serum concentration of Fluorouracil (Systemic). Monitor therapy
Fluorouracil (Topical): Gemcitabine may increase the serum concentration of Fluorouracil (Topical). 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. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). 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. Avoid combination
Warfarin: Gemcitabine may enhance the anticoagulant effect of Warfarin. Monitor therapy
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); monitor pulmonary function; signs/symptoms of capillary leak syndrome and posterior reversible encephalopathy syndrome
Frequency of adverse reactions reported for single-agent use of gemcitabine only; bone marrow depression is the dose-limiting toxicity.
>10%:
Cardiovascular: Peripheral edema (20%), edema (13%)
Central nervous system: Drowsiness (11%)
Dermatologic: Skin rash (30%), alopecia (15%)
Gastrointestinal: Nausea and vomiting (69%), diarrhea (19%), stomatitis (11%)
Genitourinary: Proteinuria (45%), hematuria (35%)
Hematologic & oncologic: Anemia (68%; grade 3: 7%; grade 4: 1%), neutropenia (63%; grade 3: 19%; grade 4: 6%), thrombocytopenia (24%; grade 3: 4%; grade 4: 1%), hemorrhage (17%; grade 3: <1%; grade 4: <1%)
Hepatic: Increased serum ALT (68%; grade 3: 8%, grade 4: 2%), increased serum AST (67%; grade 3: 6%; grade 4: 2%), increased serum alkaline phosphatase (55%; grade 3: 7%; grade 4: 2%), increased serum bilirubin (13%; grade 3: 2%, grade 4: <1%)
Infection: Infection (16%)
Renal: Increased blood urea nitrogen (16%)
Respiratory: Dyspnea (23%; grade 3: 3%; grade 4: <1%), flu-like symptoms (19%)
Miscellaneous: Fever (41%)
1% to 10%:
Central nervous system: Paresthesia (10%; grade 3: <1%)
Local: Injection site reaction (4%)
Renal: Increased serum creatinine (8%)
Respiratory: Bronchospasm (<2%)
<1% (Limited to important or life-threatening; reported with single-agent use or with combination therapy): Adult respiratory distress syndrome, anaphylactoid reaction, anorexia, arthralgia, bullous skin disease, capillary leak syndrome, cardiac arrhythmia, cardiac failure, cellulitis, cerebrovascular accident (Kuenen 2002), constipation, desquamation, digital vasculitis, gangrene of skin or other tissue, hemolytic-uremic syndrome, hepatic failure, hepatic veno-occlusive disease, hepatotoxicity (rare), hyperglycemia, hypertension, hypocalcemia, hypotension, increased gamma-glutamyl transferase, interstitial pneumonitis, myocardial infarction, neuropathy, petechiae (Nishijima 2013; Zupancic 2007), pruritus (Curtis 2014), pulmonary edema, pulmonary fibrosis, radiation recall phenomenon, renal failure, respiratory failure, reversible posterior leukoencephalopathy syndrome, sepsis, supraventricular cardiac arrhythmia, thrombotic thrombocytopenic purpura (Nishijima 2013; Zupancic 2007)
The lower clearance in elderly patients results in higher concentrations of gemcitabine for any given dose.
The lower clearance in women results in higher concentrations of gemcitabine for any given dose.
Concerns related to adverse effects:
- Bone marrow suppression: May cause bone marrow suppression (neutropenia, thrombocytopenia, and anemia); myelosuppression is generally the dose-limiting toxicity and is increased when used in combination with other chemotherapy. Monitor blood counts; dosage adjustments are frequently required.
- Capillary leak syndrome: Capillary leak syndrome (CLS) with serious consequences has been reported, both with single-agent gemcitabine and with combination chemotherapy; discontinue if CLS develops.
- Hemolytic uremic syndrome: Hemolytic uremic syndrome (HUS) has been reported; may lead to renal failure and dialysis (including fatalities); monitor for evidence of anemia with microangiopathic hemolysis (elevation of bilirubin or LDH, reticulocytosis, severe thrombocytopenia, and/or renal failure) and monitor renal function at baseline and periodically during treatment. Permanently discontinue if HUS or severe renal impairment occurs; renal failure may not be reversible despite discontinuation.
- Hepatotoxicity: Serious hepatotoxicity (including liver failure and death) has been reported (when used alone or in combination with other hepatotoxic medications); use in patients with hepatic impairment (history of cirrhosis, hepatitis, or alcoholism) or in patients with hepatic metastases may lead to exacerbation of hepatic impairment. Monitor hepatic function at baseline and periodically during treatment; consider dose adjustments with elevated bilirubin; discontinue if severe liver injury develops.
- Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported, both with single-agent therapy and with combination chemotherapy. PRES may manifest with blindness, confusion, headache, hypertension, lethargy, seizure, and other visual and neurologic disturbances. If PRES diagnosis is confirmed (by MRI), discontinue therapy.
- Pulmonary toxicity: Pulmonary toxicity, including adult respiratory distress syndrome, interstitial pneumonitis, pulmonary edema, and pulmonary fibrosis, has been observed; may lead to respiratory failure (some fatal) despite discontinuation. Onset for symptoms of pulmonary toxicity may be delayed up to 2 weeks beyond the last dose. Discontinue for unexplained dyspnea (with or without bronchospasm) or other evidence of pulmonary toxicity.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Radiation therapy recipients: Not indicated for use with concurrent radiation therapy; radiation toxicity, including tissue injury, severe mucositis, esophagitis, or pneumonitis, has been reported with concurrent and nonconcurrent administration; has radiosensitizing activity when gemcitabine and radiation therapy are given together or ≤7 days apart; radiation recall may occur when gemcitabine and radiation therapy are given >7 days apart.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Other warnings/precautions:
- Infusion duration/frequency: Prolongation of the infusion duration >60 minutes or more frequent than weekly dosing have been shown to alter the half-life and increase toxicity (hypotension, flu-like symptoms, myelosuppression, weakness). A fixed-dose rate (FDR) infusion rate of 10 mg/m2/minute has been studied in adults in order to optimize the pharmacokinetics (off-label); prolonged infusion times increase the intracellular accumulation of the active metabolite, gemcitabine triphosphate (Ko, 2006; Tempero, 2003). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ko, 2006; Poplin, 2009).
D
Adverse events were observed in animal reproduction studies. May cause fetal harm if administered during pregnancy; adverse effects in reproduction are anticipated based on the mechanism of action.
A pyrimidine antimetabolite that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase, cell cycle-specific for the S-phase of the cycle (also blocks cellular progression at G1/S-phase). 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.
Widely distributed into tissues; present in ascitic fluid; Vd: Infusions <70 minutes: 50 L/m2; Long infusion times (70-285 minutes): 370 L/m2
Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites
Urine (92% to 98%; primarily as inactive uracil metabolite); feces (<1%)
30 minutes after completion of infusion
Gemcitabine: Infusion time ≤70 minutes: 42 to 94 minutes; infusion time 3 to 4 hours: 4 to 10.5 hours (affected by age and gender)
Metabolite (gemcitabine triphosphate), terminal phase: 1.7 to 19.4 hours
Negligible
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience flu-like symptoms, nausea, vomiting, diarrhea, lack of appetite, constipation, mouth sores, hair loss, loss of strength and energy, headache, or fatigue. Have patient report immediately to prescriber signs of infection, signs of capillary leak syndrome (abnormal heartbeat; angina; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; urinary retention or change in amount of urine passed; hematuria), signs of posterior reversible encephalopathy syndrome (confusion, not alert, vision changes, seizures, or severe headache), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of high blood sugar (confusion, feeling sleepy, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), signs of Hemolytic-uremic syndrome (urinary retention; loss of strength and energy; signs of bleeding or bruising; fever; or swelling of the face, hands, feet, or body), severe dizziness, passing out, shortness of breath, burning or numbness feeling, or severe injection site burning, redness, edema, pain, or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.