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Deoxycytidine antimetabolite nucleoside inhibitorUsed for breast cancer, non-small cell lung cancer (NSCLC), ovarian cancer, and pancreatic cancerIncreased toxicities occur with infusion times longer than 60 minutes or with dosing more than once weekly
Gemcitabine/Gemcitabine Hydrochloride Intravenous Inj Sol: 1mL, 38mg, 100mgGemcitabine/Gemcitabine Hydrochloride/Gemzar Intravenous Inj Pwd F/Sol: 1g, 2g, 200mg
1,000 mg/m2 IV over 30 minutes followed by cisplatin 100 mg/m2 IV on day 1, then gemcitabine 1,000 mg/m2 IV over 30 minutes on days 8 and 15, repeated every 4 weeks. Alternatively, give gemcitabine 1,250 mg/m2 IV over 30 minutes followed by cisplatin 100 mg/m2 IV on day 1, then gemcitabine 1,250 mg/m2 IV over 30 minutes on day 8, repeated every 3 weeks. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on the day of therapy. In a multinational, randomized clinical trial, patients with inoperable Stage IIIA, IIIB, or IV NSCLC treated with gemcitabine and cisplatin every 4 weeks (n = 260) had increased median overall survival (9 months vs. 7.6 months; p = 0.008) and longer median time to disease progression (5.2 months vs. 3.7 months; p = 0.009) than those patients treated with cisplatin alone (n = 262); additionally, the tumor response rate was 26% for patients who received combination therapy compared with 10% in patients treated with cisplatin alone. In another multicenter, randomized clinical trial, patients with Stage IIIB or IV NSCLC were treated with gemcitabine plus cisplatin (n = 69) or etoposide plus cisplatin (n = 66) every 21 days. In this trial, there was no difference in overall survival (8.7 months vs. 7 months; p = 0.18); however, the median time to disease progression was 5 months in patients treated with gemcitabine plus cisplatin compared with 4.1 months in those who received etoposide plus cisplatin (p = 0.015). The objective response rate was 33% compared with 14% (p = 0.01), respectively.
1,200 mg/m2 IV on days 1 and 8 in combination with carboplatin (AUC 5 IV) on day 1, every 21 days for 6 cycles. Alternatively, gemcitabine 1,000 mg/m2 IV on days 1, 8 and 15 in combination with carboplatin (AUC 5 IV) on day 1, repeated every 28 days for 4 cycles or, gemcitabine 1,000 mg/m2 IV on days 1 and 8 in combination with carboplatin (AUC 5 IV) on day 1, repeated every 21 days for 4 cycles, have also been studied.
Gemcitabine 1,000 mg/m2 IV on days 1 and 8 in combination with paclitaxel 200 mg/m2 IV on day 1, every 3 weeks has been given. Alternately, gemcitabine 1,250 mg/m2 IV on days 1 and 8 in combination with paclitaxel 175 mg/m2 IV on day 1, every 3 weeks has also been given.
1,000 or 1,100 mg/m2 IV days 1 and 8 in combination with docetaxel day 1 repeated every 21 days (GD regimen) has been studied. In a phase III trial of 311 patients with Stage IIIB or IV NSCLC, GD (gemcitabine dose, 1,000 mg/m2) was compared to cisplatin/vinorelbine (CV). Progression-free survival (4.2 months vs. 4 months) and overall survival (11.1 months vs. 9.6 months) were not significantly different between the 2 arms. Grade 3 and 4 febrile neutropenia, anemia and gastrointestinal toxicities were all significantly higher with CV, while fluid retention and grade 3 or 4 pulmonary events were greater with GD. In another phase III trial of 413 patients comparing GD (gemcitabine dose, 1,000 mg/m2) to CV, no difference in overall survival, the primary endpoint, was observed (9 months vs. 9.7 months). Grade 3 and 4 neutropenia and nausea/vomiting occurred more frequently with CV. In a phase III trial of 312 patients, GD (gemcitabine dose, 1,100 mg/m2) was compared to single-agent docetaxel. Overall survival, the primary endpoint, was significantly improved in the combination arm (9.4 months vs. 8.3 months, p = 0.037).
1,000 mg/m2 IV on days 1 and 15 in combination with topotecan (1 mg/m2 IV on days 1, 2, 3, 4, and 5). The cycle was repeated every 28 days. In a phase II study of 51 patients with previously untreated advanced NSCLC, 17% of patients had a partial response while 23% had stable disease. The 1-year survival rate was 39% with median survival of 7.6 months.
400 mg/m2 IV on days 1 and 5 in combination with topotecan (0.75 mg/m2 IV on days 1, 2, 3, 4, and 5). The cycle was repeated every 21 days. In a phase II trial, 35 patients with advanced non-small cell lung cancer received topotecan/gemcitabine in the second-line setting. Partial response was observed in 11% of patients while 23% had stable disease. Of 17 patient with refractory disease, the partial response rate was 18%, and 18% had stable disease. For all patients, the median survival was 7 months with a 1-year survival rate of 20%.
1,000 mg/m2 IV over 30 minutes once weekly for up to 7 consecutive weeks, followed by 1 week of rest. After week 8, administer gemcitabine 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15, repeated every 28 days. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on the day of therapy. In a randomized, single-blind, active-controlled clinical trial, patients with treatment naive locally advanced or metastatic pancreatic cancer were treated with either gemcitabine (n = 63) or 5-FU (n = 63). Clinical benefit response (defined as a reduced pain intensity or analgesic consumption of at least 50% or a 20-point or greater improvement in Karnofsky score for at least 4 weeks without worsening in other parameters, OR stable pain and performance status, with a sustained weight gain of at least 7% that was sustained for 4 weeks or longer, not due to fluid accumulation) was significantly improved in patients who received gemcitabine compared with 5-FU (22.2% vs. 4.8%; p = 0.004). Additionally, median overall survival (5.7 vs. 4.2 months; p = 0.0009) and time to disease progression (2.1 vs. 0.9 months; p = 0.0013) were significantly improved in patients treated with gemcitabine.
1,000 mg/m2 IV over 30 minutes once weekly for up to 7 consecutive weeks, followed by 1 week of rest, in combination with erlotinib 100 mg by mouth once daily on an empty stomach. After week 8, continue erlotinib and administer gemcitabine 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15, repeated every 28 days until disease progression or unacceptable toxicity. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on the day of therapy. In a randomized, double-blind, placebo-controlled clinical trial, patients with locally advanced, unresectable, or metastatic pancreatic cancer were treated with gemcitabine in combination with either erlotinib (n = 285) or placebo (n = 284). Combination with erlotinib improved overall survival (6.4 vs. 6 months; HR 0.81; p = 0.028) and progression-free survival (PFS) (3.8 vs. 3.5 months; HR 0.76; p = 0.006) compared with placebo; 1-year survival was 23.8% vs. 19.4%, respectively. A tumor response (complete response plus partial response) was observed in 8.6% of patients treated with gemcitabine plus erlotinib and in 7.9% of those who received gemcitabine and placebo (p = 0.87); the median duration of response was 23.9 weeks and 23.3 weeks, respectively.
1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15 every 28 days for 6 cycles. In a phase III trial, 368 patients with previously untreated pancreatic cancer were randomized to receive gemcitabine or observation after complete surgical resection. Disease-free survival (13.4 months vs. 6.9 months, p < 0.001), the primary endpoint, and overall survival (22.8 months vs. 20.2 months, p = 0.005) were significantly longer in the gemcitabine arm. In another phase III trial, 442 patients with surgically resected pancreatic cancer were randomized to receive gemcitabine before and after 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) or 5-FU before and after 5-FU-based CRT. Beginning 3 to 8 weeks after surgery, gemcitabine patients received 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15, followed in 1 to 2 weeks by 5.5 weeks of 5-FU-based CRT, which was followed in 3 to 5 weeks by gemcitabine 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15, every 28 days for 3 additional cycles. The prospective primary endpoints of the study were overall survival (OS) and OS in patients with tumors of the pancreatic head. No significant difference was observed in OS for the total treatment population, however patients with tumors confined to the pancreatic head (n = 330) did experience a significantly longer OS in the gemcitabine arm (20.6 months vs. 16.9 months, p = 0.003). Grade 4 hematologic toxicities were significantly greater in patients treated with gemcitabine (14% vs. 2%, p < 0.0001).
1,000 mg/m2 IV over 100 minutes (10 mg/m2/minute) on day 1 in combination with oxaliplatin (100 mg/m2 IV on day 2), repeated every 2 weeks until disease progression or unacceptable toxicity. In a phase III study of 313 patients with untreated locally advanced and metastatic unresectable pancreatic cancer, oxaliplatin and gemcitabine (GemOx) were compared to gemcitabine alone (given over 30 minutes). The primary endpoint of overall survival was not significantly different between the 2 treatments. Seventy-four percent of patients in the gemcitabine arm crossed-over to receive gemcitabine and platinum combinations at disease progression, possibly limiting this variable. Response rate and progression-free survival were each significantly better with GemOx, 26.8% and 5.8 months, as compared to gemcitabine, 17.3% and 3.7 months. In addition, clinical benefit response was greater in patients who received GemOx than gemcitabine, 38.2% vs. 26.9% (p = 0.03). In another phase III trial, 833 patients with previously untreated locally advanced and metastatic unresectable pancreatic cancer were randomized to receive GemOx, fixed-dose rate gemcitabine (1500 mg/m2 IV infusion on days 1, 8, and 15 of a 28-day cycle, administered at a rate of 10 mg/m2/minute IV), or 30-minute IV infusions of gemcitabine (1,000 mg/m2 IV weekly for 7 weeks, in week 9 administration on days 1, 8, and 15 every 28 days). Neither GemOx (5.7 months) or fixed-dose-rate gemcitabine (6.2 months) produced a statistically significant difference in overall survival compared to gemcitabine as a 30-minute infusion (4.9 months). Grade 3 or 4 neutropenia and thrombocytopenia occurred more frequently in the gemcitabine fixed-dose rate arm; grade 3 or 4 sensory neuropathy occurred more frequently with GemOx.
1,000 mg/m2 IV over 30 to 40 minutes on days 1, 8, and 15 preceded by nab-paclitaxel (125 mg/m2 IV over 30 to 40 minutes on days 1, 8, and 15) every 28 days. In a multinational, randomized, open-label study, nab-paclitaxel plus gemcitabine (n = 431) was compared to gemcitabine 1,000 mg/m2 IV weekly for 7 weeks with a 1 week rest period in cycle 1, and then on days 1, 8, and 15 of each subsequent 28 day cycle (n = 430) until disease progression or unacceptable toxicity in patients with metastatic adenocarcinoma of the pancreas. Median overall survival (8.5 months vs. 6.7 months; HR 0.72; p < 0.001) and median progression free survival (5.5 months vs. 3.7 months; HR 0.69; p < 0.001) were improved by the combination of nab-paclitaxel and gemcitabine. Additionally, 23% of patients treated with combination therapy had a confirmed complete or partial overall response, compared to 7% of patients treated with gemcitabine alone (p < 0.001).
1,000 mg/m2 IV on days 1, 8, and 15, plus capecitabine (1,660 mg/m2 orally on days 1 to 21 followed by 7 days of rest), repeated every 28 days for 6 cycles. After a median follow-up of 43.2 months, patients who underwent complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection) and were treated with gemcitabine plus capecitabine had significantly longer median overall survival compared with those receiving gemcitabine alone (28 months vs. 25.5 months; HR 0.82; p = 0.032) in a multicenter, randomized, open-label phase 3 clinical trial. In a subgroup analysis, the magnitude of effect on median overall survival in patients with R0 resection (39.5 months vs. 27.9 months) was greater than in patients with R1 resection (23.7 months vs. 23 months) (X2 14.83; p = 0.0001).
1,250 mg/m2 IV over 30 minutes, preceded by paclitaxel 175 mg/m2 IV over 3 hours, on day 1, then gemcitabine 1,250 mg/m2 IV over 30 minutes on day 8, repeated every 21 days. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on day 8 of therapy. In a randomized trial, gemcitabine plus paclitaxel was compared to paclitaxel alone in patients with metastatic breast cancer who had received prior adjuvant/neoadjuvant chemotherapy (unless clinically contraindicated). The combination therapy resulted in statistically significant improvement in time to documented disease progression (5.2 vs. 2.9 months; p < 0.0001) and overall response rate (40.6% vs. 22.1%; p < 0.0001) as compared to paclitaxel alone. Gemcitabine plus paclitaxel also showed a strong trend toward improved survival based on an interim survival analysis.
1,200 to 1,250 mg/m2 IV on days 1, 8, and 15, every 28 days; overall response rate was 16% to 29% in patients who had previously received at least 1 other chemotherapy.
1,000 mg/m2 IV on days 1, 8, and 15, every 28 days or 1,000 mg/m2 IV on days 1 and 8, every 21 days have been given. In 2 phase III trials, time to progression in one study and progression free survival in the other were similar to liposomal doxorubicin.
1,000 mg/m2 IV over 30 minutes followed by carboplatin AUC 4 IV on day 1, then gemcitabine 1,000 mg/m2 IV over 30 minutes on day 8, repeated every 21 days. Gemcitabine doses should be adjusted for hematologic toxicity based upon the granulocyte and platelet counts taken on day 8 of therapy. In a phase III trial, 356 patients with relapsed ovarian cancer at least 6 months after primary platinum therapy were randomized to gemcitabine 1,000 mg/m2 IV on days 1 and 8 plus carboplatin (AUC 4) on day 1 or carboplatin (AUC 5) single agent therapy, both given as a 21-day cycle. Progression-free survival (PFS) was 8.6 months for patients treated with gemcitabine/carboplatin therapy vs. 5.8 months for those treated with single agent carboplatin (p = 0.0038). Overall survival was not different between the 2 arms (18 months for combination therapy vs. 17.3 months for single agent carboplatin). Other phase II trials have reported results of gemcitabine in combination with other agents (e.g., cisplatin, liposomal doxorubicin, or topotecan). In one trial of 42 patients with advanced ovarian cancer, gemcitabine 1250 mg/m2 IV on day 1 and 8 of a 21-day cycle was given in combination with cisplatin (75 mg/m2 IV on day 1 prior to gemcitabine) as first line therapy. Per an intent-to-treat analysis, the overall response rate was 57.1%. After a median follow-up of 15.8 months, the median survival was 24 months and the median PFS was 13.4 months.
1,000 mg/m2 IV on days 1 and 8 in combination with cisplatin (25 mg/m2 IV on days 1 and 8) every 21 days for 8 cycles. In a phase III trial, 410 patients with advanced cholangiocarcinoma, gallbladder cancer, or ampullary cancer were randomized to receive gemcitabine with or without cisplatin. Overall survival, the primary endpoint, was significantly greater in the combination treatment arm (11.7 months vs. 8.1 months). Median progression-free survival was also significantly greater in the combination treatment arm (8 months vs. 5 months). Grade 3 or 4 neutropenia (25.3% vs. 16.6%) and anemia (7.6% vs. 3%) occurred significantly more often with combination therapy. Overall incidence of grade 3 or 4 toxicities were not significantly different between the two treatment arms (70.7% vs. 68.8%). Additional trials have shown a benefit for gemcitabine/cisplatin compared to cisplatin alone.
1,000 mg/m2 IV over 30 to 60 minutes on days 1, 8, and 15 plus cisplatin 70 mg/m2 on day 2 repeated every 28 days (GC regimen) for up to 6 cycles was compared with methotrexate 30 mg/m2 on days 1, 15, and 22, vinblastine 3 mg/m2 IV on days 2, 15, and 22, doxorubicin 30 mg/m2 on day 2, and cisplatin 70 mg/m2 on day 2 (MVAC regimen) in a multicenter, randomized, phase III trial. In a long-term analysis of this study, the improvement in overall survival (OS) (14 months vs. 15.2 months) and progression-free survival (PFS) (7.7 months vs. 8.3 months) by GC was not significantly improved compared with MVAC. The 5-year OS (13% vs. 15.3%) and PFS (9.8% vs. 11.3%) rates were also nonsignificantly lower with GC compared with MVAC; however, GC was associated with significantly less grade 3 or 4 neutropenic sepsis (1% vs. 12%) and mucositis (1% vs. 22%). Treatment-related death was also reported less often in the GC arm (1% vs. 3%).
Gemcitabine 1,000 mg/m2 IV on days 1, 8, and 15 in combination with cisplatin 100 mg/m2 IV on day 1, every 28 days for 6 cycles. Alternately, gemcitabine 1,250 mg/m2 IV on days 1 and 8 in combination with cisplatin 80 mg/m2 IV on day 1, every 21 days for 6 cycles, has also been studied. Carboplatin AUC 5 IV on day 1 has been substituted for cisplatin, and given with gemcitabine 1,000 mg/m2 IV on days 1, 8, and 15, every 28 days for 6 cycles.
1,250 mg/m2 to 1,500 mg/m2 IV on days 1, 8, and 15, every 28 days has been given in phase II studies; overall response rates were low, ranging from 0 to 7%.
1,200 mg/m2 IV over 30 minutes on days 1, 8, and 15 repeated every 28 days for 3 to 6 cycles has been studied in nonrandomized, phase II trials; overall response rates ranged from 70% to 75%.
1,000 mg/m2 IV over 30 minutes on days 1 and 8 in combination with cisplatin 75 mg/m2 IV on day 1 and dexamethasone 40 mg orally daily on days 1, 2, 3, and 4 (GDP regimen) was evaluated in a randomized, phase III trial (NCIC-CTG LY.12 trial). Treatment was repeated every 21 days for 2 cycles. In patients with CD20-positive lymphoma, rituximab 375 mg/m2 IV was added on day 1 of each treatment cycle (R-GDP regimen). Patients in the trial could receive a third cycle of therapy if they did not achieve a complete or partial response after the second cycle. Patients with CD20-positive lymphoma who received an autologous stem-cell transplant (ASCT) were randomized to receive either rituximab 375 mg/m2 IV every 2 months for 6 cycles or observation starting 28 days post ASCT.
800 mg/m2 IV over 30 minutes on days 1 and 8 in combination with cisplatin (25 mg/m2 IV on days 1, 2 and 3), prednisone (60 mg/m2 PO on days 1, 2, 3, 4, and 5), and thalidomide (200 mg PO daily) repeated every 21 days until disease progression or for up to 6 cycles was evaluated in patients with previously untreated PTCL in a randomized trial. Patients received aspirin 100 mg/day PO during thalidomide therapy. The use of granulocyte colony-stimulation factor was permitted as indicated.
†Indicates off-label use
The suggested maximum tolerated dose (MTD) for gemcitabine is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state. Therefore, dosing may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.
1,250 mg/m2 IV once weekly; number of weekly doses and length of cycle is indication-specific.
Safety and efficacy have not been established.
Baseline Hepatic Impairment:Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Treatment-Related Hepatotoxicity:Severe hepatotoxicity: Permanently discontinue gemcitabine.
Baseline Renal Impairment:Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Treatment-Related Nephrotoxicity:Severe renal impairment: Permanently discontinue gemcitabine therapy.
For storage information, see the specific product information within How Supplied section. CAUTION: Observe and exercise appropriate precautions for handling, preparing, and administering cytotoxic drugs.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.Gemcitabine is available as a powder for injection, which requires reconstitution, and a solution for injection. Both formulations require further dilution prior to administration. It is also available as a premixed bag for IV infusion which does not require further dilution.
Reconstitution (powder for injection)200 mg vial: Add 5 mL of 0.9% sodium chloride for injection without preservatives to each vial, for a final concentration of 38 mg/mL. Complete withdrawal of the vial contents will provide 200 mg of gemcitabine. Shake to dissolve.1 g vial: Add 25 mL of 0.9% sodium chloride for injection without preservatives to each vial, for a final concentration of 38 mg/mL. Complete withdrawal of the vial contents will provide 1 g of gemcitabine.Shake to dissolve.Storage after reconstitution: Reconstituted gemcitabine solutions are stable for 24 hours at room temperature (20 to 25 degrees Celsius or 68 to 77 degrees Fahrenheit). Do not refrigerate, as crystallization may occur. Discard unused portion. Intravenous infusion (reconstituted powder or solution for injection):Dilute the appropriate amount of gemcitabine (solution for injection or reconstituted powder for injection) in 0.9% sodium chloride injection solution; the final concentrations may be as low as 0.1 mg/mL.Mix by gentle inversion. Do not shake.Storage after dilution: Diluted gemcitabine solutions are stable for 24 hours at controlled room temperature (20 to 25 degrees Celsius or 68 to 77 degrees Farenheit). Discard unused portion. Administration:The manufacturer recommends infusing over 30 minutes. In clinical trials where the infusion time was more than 60 minutes, or the frequency was more than once weekly, there was an increased incidence of clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia. However, in one clinical trial, gemcitabine was safely administered over 100 minutes (10 mg/m2/min) in combination with oxaliplatin in the treatment of advanced pancreatic cancer.
Premixed Infusion Bag:NOTE: Use another formulation of gemcitabine for patients who require a dose less than 1,150 mg.Do not dilute prior to administration.Do not remove or add medication.Select the premixed bag based on the patient's BSA range; the administered dose may vary from the BSA-calculated dose by no more than 5%. For doses of 1,000 mg/m2 (Indications: Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer):BSA 1.16 to 1.25: 1,200 mg infusion bagBSA 1.26 to 1.35: 1,300 mg infusion bagBSA 1.36 to 1.45: 1,400 mg infusion bagBSA 1.46 to 1.55: 1,500 mg infusion bagBSA 1.56 to 1.65: 1,600 mg infusion bagBSA 1.66 to 1.75: 1,700 mg infusion bagBSA 1.76 to 1.85: 1,800 mg infusion bagBSA 1.86 to 1.95: 1,900 mg infusion bagBSA 1.96 to 2.1: 2,000 mg infusion bagBSA 2.11 to 2.3: 2,200 mg infusion bagBSA 2.31 to 2.45: 2,400 mg (e.g., 2 x 1,200 mg infusion bags)BSA 2.46 to 2.55: 2,500 mg (e.g., 1,200 mg infusion bag plus 1,300 mg infusion bag)BSA 2.56 to 2.64: 2,600 mg (e.g., 2 x 1,300 mg infusion bags) For doses of 1,250 mg/m2 (Indications: Non-Small Cell Lung Cancer, Breast Cancer):BSA 1.16 to 1.24: 1,500 mg infusion bagBSA 1.25 to 1.32: 1,600 mg infusion bagBSA 1.33 to 1.4: 1,700 mg infusion bagBSA 1.41 to 1.47: 1,800 mg infusion bagBSA 1.48 to 1.56: 1,900 mg infusion bagBSA 1.57 to 1.68: 2,000 mg infusion bagBSA 1.69 to 1.84: 2,200 mg infusion bagBSA 1.85 to 1.96: 2,400 mg (e.g., 2 x 1,200 mg infusion bags)BSA 1.97 to 2.04: 2,500 mg (e.g., 1,200 mg infusion bag plus 1,300 mg infusion bag)BSA 2.05 to 2.12: 2,600 mg (e.g., 2 x 1,300 mg infusion bags)BSA 2.13 to 2.2: 2,700 mg (e.g., 1,200 mg infusion bag plus 1,500 mg infusion bag)BSA 2.21 to 2.28: 2,800 mg (e.g., 2 x 1,400 mg infusion bags)BSA 2.29 to 2.36: 2,900 mg (e.g., 1,200 mg infusion bag plus 1,700 mg infusion bag)BSA 2.37 to 2.44: 3,000 mg (e.g., 2 x 1,500 mg infusion bags)BSA 2.45 to 2.52: 3,100 mg (e.g., 1,200 mg infusion bag plus 1,900 mg infusion bag)BSA 2.53 to 2.6: 3,200 mg (e.g., 2 x 1,600 mg infusion bags)BSA 2.61 to 2.64: 3,300 mg (e.g., 1,600 mg infusion bag plus 1,700 mg infusion bag) Administration: Infuse the total dose 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.
Generic:- Discard entered multi-dose vial after 28 days- Discard product if it contains particulate matter, is cloudy, or discolored- Do not refrigerate- Store at controlled room temperature (between 68 and 77 degrees F)Gemzar:- Discard unused portion. Do not store for later use.- Do not refrigerate- Reconstituted product is stable for 24 hours at room temperature- Store unreconstituted product at 68 to 77 degrees F
Myelosuppression, including neutropenia, thrombocytopenia, and anemia, has occurred with gemcitabine therapy; the risk is increased when used in combination with other chemotherapeutic agents. Monitor a CBC plus differential prior to each dose of gemcitabine; a dose reduction or interruption of therapy may be necessary. Patients with an active infection should be treated prior to receiving gemcitabine. Patients should immediately report any symptoms of severe myelosuppression such as fever, sore throat, or abnormal bleeding.
Gemcitabine is not recommended for use in combination with radiation therapy due to the risk of excessive toxicity. In a clinical trial of patients with non-small cell lung cancer (NSCLC) receiving concurrent (given together or 7 days or less apart) gemcitabine and thoracic radiation therapy, life-threatening mucositis, esophagitis, and pneumonitis were reported. Excessive toxicity has not been observed when gemcitabine is administered more than 7 days before or after radiation (nonconcurrent); however, radiation recall has occurred in patients who have received gemcitabine after prior radiation.
Gemcitabine should be used cautiously in patients with pre-existing hepatic disease, as treatment in patients with concurrent liver metastases or a history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency. Treatment-related hepatotoxicity has occurred with gemcitabine use, either as monotherapy or in combination with other potentially hepatotoxic drugs; some cases resulted in liver failure and death. Assess liver function tests prior to initiation of gemcitabine therapy and periodically during treatment; permanently discontinue gemcitabine in patients that develop severe hepatotoxicity.
Prolonged infusion times beyond 60 minutes, as well as more frequent than once weekly administration, has been associated with infusion-related reactions and increased toxicity, including clinically significant hypotension, severe flu-like symptoms, myelosuppression, and asthenia. The half-life of gemcitabine is also prolonged and volume of distribution increased with longer infusions. The manufacturer recommends administration of gemcitabine over 30 minutes; however, it has been safely administered over 100 minutes (10 mg/m2/min) in one clinical trial of patients with advanced pancreatic cancer. Use caution if administration of gemcitabine lasts beyond 60 minutes.
Pneumonitis (interstitial lung disease, ILD), pulmonary edema, acute respiratory distress syndrome (ARDS), and pulmonary fibrosis have been observed in patients treated with gemcitabine in clinical studies; some cases have been fatal, despite discontinuation of therapy. Use gemcitabine with caution in patients with pre-existing pulmonary disease or a history of interstitial pneumonitis or pulmonary fibrosis. Permanently discontinue therapy for unexplained dyspnea (with or without bronchospasm) or other evidence of severe pulmonary toxicity. The onset of pulmonary symptoms may occur up to 2 weeks after the last dose of gemcitabine.
Hemolytic-uremic syndrome (HUS) has been reported in patients treated with gemcitabine, including some cases requiring dialysis and fatalities due to renal failure; most gemcitabine-related cases of fatal renal failure in clinical trials were due to HUS. Permanently discontinue gemcitabine in patients with HUS or severe renal impairment. Assess renal function prior to initiation of therapy with gemcitabine and periodically during treatment. Consider HUS in patients who develop anemia with evidence of microangiopathic hemolysis, elevated bilirubin or LDH, reticulocytosis, severe thrombocytopenia, or increased serum creatinine/BUN (renal impairment). Renal failure may not be reversible, even after discontinuation of therapy.
Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), has been reported in patients treated with gemcitabine, either as monotherapy or in combination with other chemotherapeutic agents. Permanently discontinue gemcitabine in patients suspected of developing PRES. Patients with headache, lethargy, seizures, confusion, blindness, and other visual or neurologic disturbances should be evaluated for RPLS with magnetic resonance imaging (MRI). Mild to severe hypertension may also be present.
The safety and efficacy of gemcitabine have not been established in children. In a trial of pediatric patients with refractory leukemia, the maximum tolerated dose was 10 mg/m2 per minute for 360 minutes weekly for 3 weeks, followed by one week of rest. This dose of gemcitabine was administered to pediatric patients with acute lymphoblastic leukemia (ALL; n = 22) and acute myelogenous leukemia (AML; n = 10); one additional four-week course could be administered to patients with M1 or M2 bone marrow on day 28 who did not experience unacceptable toxicity. Observed toxicities included bone marrow suppression, febrile neutropenia, elevated transaminases, nausea, and rash/desquamation. No meaningful clinical activity was observed in this trial.
Gemcitabine toxicity may occur earlier on therapy or with a higher frequency in geriatric patients and females, as a result of slower drug clearance leading to higher plasma and intracellular concentrations of gemcitabine and increased half-life at any dose. These patients require close monitoring during gemcitabine therapy and dose modification may be necessary. In clinical studies of patients with various cancers treated with gemcitabine monotherapy (n = 979), patients aged 65 and older had a higher rate of grade 3 or 4 thrombocytopenia compared with younger patients, although there were no overall differences in safety. In another randomized trial of women with ovarian cancer treated with gemcitabine in combination with carboplatin (n = 175), patients 65 years of age or older experienced significantly higher grade 3 or 4 neutropenia compared to younger patients; efficacy was similar between older and younger patients. Additionally, in studies of gemcitabine monotherapy, women (especially older women) were less likely to proceed to subsequent cycles of treatment, and were more likely to experience grade 3 or 4 neutropenia and thrombocytopenia.
Gemcitabine is classified as FDA pregnancy category D. Although there are no adequate and well-controlled studies in pregnant women, gemcitabine is expected to cause fetal harm based on animal data and its mechanism of action. If gemcitabine is used during pregnancy or if a woman becomes pregnant during therapy, the patient should be apprised of the risk to the fetus. Two case reports described gemcitabine administration to pregnant women in the second trimester or later. In one case, a woman with lung cancer was administered gemcitabine and carboplatin at 25 weeks gestation. The baby was delivered at 28 weeks by elective cesarean. The baby had multiple complications from prematurity, but the authors speculated that chronic lung disease and excessive lung secretions may have been due to gemcitabine or the malignancy. At 8 months of age, the infant was successfully weaned from oxygen therapy and had age-appropriate neurodevelopment. The other case report described a pregnant woman with lung cancer who received gemcitabine in combination with cisplatin (weeks 19 to 25), in addition to cisplatin and docetaxel (weeks 9 to 18); the infant was delivered by cesarean at 33 weeks. An extensive workup of the infant failed to find any abnormalities and the infant was developing normally at 10 months of age. In animal studies, gemcitabine was embryotoxic in mice at doses approximately 0.005 times the recommended human dose on a mg/m2 basis, causing fetal malformations such as cleft palate and incomplete ossification. It was fetotoxic in rabbits at doses approximately 0.002 times the recommended human dose on a mg/m2 basis, resulting in fetal malformations such as fused pulmonary artery and absence of the gall bladder; embryotoxicity also occurred, including decreased fetal viability, reduced live litter sizes, and developmental delays.
Counsel patients about the reproductive risk and contraception requirements during gemcitabine treatment. Gemcitabine can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during treatment with gemcitabine and for 6 months after the last dose; males with female partners of reproductive potential should use effective contraception during and for at least 3 months after treatment with gemcitabine. Females of reproductive potential should undergo pregnancy testing prior to initiation of gemcitabine. Women who become pregnant while receiving gemcitabine should be apprised of the potential hazard to the fetus. Based on animal studies, gemcitabine may cause infertility in males of reproductive potential.
Due to the potential for serious adverse reactions in nursing infants from gemcitabine, advise women to discontinue breast-feeding during treatment and for at least 1 week after the final dose. It is not known whether gemcitabine is present in human milk, although many drugs are excreted in human milk.
lymphopenia / Delayed / 0-43.0vomiting / Early / 2.0-39.0nausea / Early / 1.0-39.0neutropenia / Delayed / 25.0-25.0alopecia / Delayed / 0-18.0azotemia / Delayed / 0-16.0elevated hepatic enzymes / Delayed / 8.0-10.0anemia / Delayed / 8.0-8.0fatigue / Early / 0-7.0constipation / Delayed / 0-7.0hypomagnesemia / Delayed / 0-7.0infection / Delayed / 0-5.0thrombocytopenia / Delayed / 5.0-5.0stomatitis / Delayed / 0-4.0dyspnea / Early / 0-4.0hyperglycemia / Delayed / 0-4.0hyperbilirubinemia / Delayed / 0-3.0drowsiness / Early / 0-2.0pharyngitis / Delayed / 0-2.0fever / Early / 0-2.0bronchospasm / Rapid / 0-2.0bleeding / Early / 0-2.0hypocalcemia / Delayed / 0-2.0diarrhea / Early / 1.0-1.0rash / Early / 0-1.0hematuria / Delayed / 0-1.0proteinuria / Delayed / 0-1.0hypotension / Rapid / 0-1.0capillary leak syndrome / Early / 0-1.0paresthesias / Delayed / 0-1.0hemolytic-uremic syndrome / Delayed / 0.3-0.3renal failure (unspecified) / Delayed / Incidence not knownhepatotoxicity / Delayed / Incidence not knownhepatic failure / Delayed / Incidence not knownsinusoidal obstruction syndrome (SOS) / Delayed / Incidence not knownveno-occlusive disease (VOD) / Delayed / Incidence not knownenterocolitis / Delayed / Incidence not knownrenal tubular necrosis / Delayed / Incidence not knownvasculitis / Delayed / Incidence not knownstroke / Early / Incidence not knownheart failure / Delayed / Incidence not knownmyocardial infarction / Delayed / Incidence not knownpulmonary fibrosis / Delayed / Incidence not knownacute respiratory distress syndrome (ARDS) / Early / Incidence not knownpulmonary edema / Early / Incidence not knownencephalopathy / Delayed / Incidence not knownvisual impairment / Early / Incidence not knownseizures / Delayed / Incidence not knownanaphylactoid reactions / Rapid / Incidence not known
peripheral edema / Delayed / 20.0-20.0edema / Delayed / 0-13.0bullous rash / Early / Incidence not knowncolitis / Delayed / Incidence not knownhemolysis / Early / Incidence not knownhypertension / Early / Incidence not knownpneumonitis / Delayed / Incidence not knownradiation recall reaction / Delayed / Incidence not knownesophagitis / Delayed / Incidence not knownconfusion / Early / Incidence not knownperipheral neuropathy / Delayed / Incidence not known
malaise / Early / 19.0-19.0anorexia / Delayed / 0-17.0headache / Early / 0-14.0injection site reaction / Rapid / 4.0-4.0chills / Rapid / Incidence not knownasthenia / Delayed / Incidence not knownrhinitis / Early / Incidence not knownmyalgia / Early / Incidence not knowninsomnia / Early / Incidence not knowndiaphoresis / Early / Incidence not knownlethargy / Early / Incidence not known
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents. Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity. Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary. It is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabine diphosphate inhibits ribonucleotide reductase, an enzyme responsible for catalyzing 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 results in initiation of apoptosis.
Gemcitabine is administered intravenously. Protein binding is negligible. The pharmacokinetics of gemcitabine are linear and are best described by a 2-compartment model. The exact sites of distribution of gemcitabine are unknown, but the distribution is affected by the duration of the infusion and gender. The volume of distribution increases with infusion length (less than 70 minutes, 50 L/m2; 70 to 285 minutes, 370 L/m2). Gemcitabine is metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Within 1 week, 92% to 98% of a dose is recovered, almost entirely in the urine; gemcitabine (less than 10%) and inactive metabolite, 2', 2'-difluorodeoxyuridine (dFdU), account for 99% of the excreted dose. The active metabolite, gemcitabine triphosphate, can be extracted from peripheral blood mononuclear cells; the terminal half-life for this metabolite from mononuclear cells ranges from 1.7 to 19.4 hours. Affected cytochrome P450 isoenzymes and drug transporters: None