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Introduction ⬇

VA Class:AN300

AHFS Class:

Generic Name(s):

Chemical Name:

Molecular Formula:

Gemcitabine hydrochloride, a synthetic pyrimidine nucleoside, is an antimetabolite antineoplastic agent.1,2,4

Uses ⬆ ⬇

[Section Outline]

Ovarian Cancer !!navigator!!

Gemcitabine is used in combination with carboplatin for the treatment of advanced ovarian epithelial cancer in patients whose disease has relapsed at least 6 months following completion of platinum-based therapy (i.e., platinum-sensitive recurrent ovarian cancer).1,5,62,63,64,65,66,73

The current indication for use of gemcitabine in the treatment of ovarian cancer is based principally on the results of an open-label, randomized, phase 3 study in 356 patients with advanced ovarian cancer whose disease had relapsed at least 6 months following completion of first-line, platinum-based therapy.1,73 Patients were randomized to receive either combination therapy with gemcitabine (1 g/m2 on days 1 and 8) and carboplatin (administered after gemcitabine on day 1 at the dose required to obtain an area under the plasma concentration-time curve [AUC] of 4 mg/mL per minute) or carboplatin alone (administered on day 1 at the dose required to obtain an AUC of 5 mg/mL per minute) on a 21-day cycle;1,73 6 cycles of therapy were administered in the absence of progressive disease or unacceptable toxicity, with up to 10 cycles administered to those who derived benefit from therapy.73 Patients who received combination therapy with gemcitabine and carboplatin had prolonged median progression-free survival (8.6 versus 5.8 months) and a higher overall response rate (47.2 versus 30.9%) than patients who received carboplatin alone; median overall survival and median duration of response were similar for both groups.1,73 Grade 3 or 4 hematologic toxicity occurred more frequently in patients receiving combination therapy with gemcitabine and carboplatin than in those receiving carboplatin alone; neutropenia was the predominant toxicity.1,73 A greater proportion of patients receiving the gemcitabine and carboplatin regimen received red blood cell (27 versus 6.7%) and platelet transfusions (8 versus 3%) compared with those who received carboplatin alone.1,73 Although use of hematopoietic growth factors was higher in the group receiving gemcitabine and carboplatin (23.6%) than in the group receiving carboplatin alone (10.1%), the incidence of febrile neutropenia was low and similar in both groups.1,73

Breast Cancer !!navigator!!

Gemcitabine is used in combination with paclitaxel for initial treatment of metastatic breast cancer following failure of adjuvant therapy with an anthracycline-containing regimen, unless such therapy was clinically contraindicated.1,74,75

The current indication for use of gemcitabine in the treatment of breast cancer is based principally on the results of an open-label, randomized, phase 3 study in 529 patients with locally recurrent or metastatic breast cancer following failure of prior adjuvant or neoadjuvant therapy with an anthracycline-containing regimen, unless such therapy was clinically contraindicated.1,74 Patients were randomized to receive either combination therapy with gemcitabine (1.25 g/m2 administered by IV infusion over 30-60 minutes on days 1 and 8) and paclitaxel (175 mg/m2 administered by IV infusion over 3 hours before gemcitabine on day 1) or paclitaxel alone (175 mg/m2 administered by IV infusion over 3 hours on day 1) in 21-day cycles;1,74 treatment was continued until disease progression, intolerable toxicity, or patient withdrawal occurred.74 Patients who received combination therapy with gemcitabine and paclitaxel had longer median overall survival (18.6 versus 15.8 months), median time to disease progression (6.14 versus 3.98 months), and median progression-free survival (5.9 versus 3.9 months), and a higher overall response rate (41.4 versus 26.2%) than patients who received paclitaxel alone; median duration of response was similar for both groups.74 Hematologic toxicity, particularly grade 3/4 neutropenia (47.9 versus 11.5%), was observed more frequently in patients receiving combination therapy with gemcitabine and paclitaxel than in those receiving paclitaxel alone.1,74 Febrile neutropenia occurred in 5% of patients who received combination therapy with gemcitabine and paclitaxel and in 1.2% of those who received paclitaxel alone.1,74

Pancreatic Cancer !!navigator!!

Gemcitabine is used for the palliative treatment of locally advanced (nonresectable stage II or III) or metastatic (stage IV) adenocarcinoma of the pancreas.1,5 The drug can be used either as first-line therapy1,10,57 or as second-line therapy in patients previously treated with fluorouracil.1,11 Pancreatic cancer rarely is curable,6,7 and response to conventional chemotherapy, radiation therapy, and/or surgery generally is poor regardless of the stage of the cancer.6,7 Therefore, the principal goal of therapy for pancreatic cancer generally has been to provide palliation of associated symptoms (e.g., pain) and improvement in the quality of life.1,6,7,13

The current indication for use of gemcitabine in the treatment of pancreatic cancer is based on limited data from a multicenter randomized study comparing the drug with fluorouracil in patients with locally advanced or metastatic pancreatic cancer who had not received previous chemotherapy, and from a multicenter open-label study in patients with advanced pancreatic cancer who previously had received fluorouracil alone or as a component of a chemotherapeutic regimen.1,11,57 In both clinical trials, gemcitabine was administered in an initial cycle of 1 g/m2 IV over 30 minutes once weekly for up to 7 weeks (as tolerated) followed by a treatment-free week, and in subsequent cycles of once-weekly doses (adjusted according to hematologic tolerance) for 3 consecutive weeks each month.1,11,57 The primary efficacy parameter in these studies involved palliative effects grouped as “clinical benefit response.”1,11,13,57 A clinical benefit response was defined as a reduction in pain intensity or analgesic consumption of at least 50% or an improvement in performance status of at least 20 points (on the Karnofsky scale) for a period of at least 4 consecutive weeks, without sustained worsening in any other parameter, or as a stabilization of these parameters combined with a marked, sustained weight gain (of at least 7% maintained for at least 4 weeks) that was not attributable to fluid accumulation.1,11,13,57

In the comparative study, gemcitabine therapy was associated with statistically significant increases in clinical benefit response (occurring in 23.8 versus 4.8% of patients receiving gemcitabine or fluorouracil, respectively),57 survival (median of 5.65 versus 4.41 months with gemcitabine or fluorouracil therapy, respectively), and time to disease progression (9 versus 4 weeks, respectively)57 compared with fluorouracil therapy (administered IV over 30 minutes at a weekly dosage of 600 mg/m2).1,57 However, there was no confirmed objective evidence of tumor response nor of weight gain with either therapy in this study.1 One-year survival probability based on Kaplan-Meier estimates was 18 or 2% for those receiving gemcitabine or fluorouracil, respectively.1,57

In the open-label study, 27% of patients receiving gemcitabine as second-line therapy after previous fluorouracil-containing regimens exhibited a clinical benefit response.1,11 The median duration of clinical benefit response was 14 weeks (range: 4-69 weeks), and median survival in this study was 3.9 months.1,11

Non-small Cell Lung Cancer !!navigator!!

Combination Therapy

Gemcitabine is used in combination with cisplatin for the initial treatment of inoperable, locally advanced (stage IIIA or IIIB) or metastatic (stage IV) non-small cell lung cancer.1,5,27,28,54,58,68

A small survival benefit has been demonstrated for the use of platinum-based (cisplatin) chemotherapy in selected patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have a good performance status.54,55 Platinum-based chemotherapy regimens currently are preferred for the treatment of non-small cell lung cancer.5,52,55 (See Uses: Non-small Cell Lung Cancer in Cisplatin 10:00 for comprehensive discussion.) Use of chemotherapy for the treatment of advanced non-small cell lung cancer generally is advised only in patients with good performance status (ECOG performance status of 0 or 1, and 2 in selected patients) and evaluable lesions so that treatment can be discontinued if the disease does not respond.52 The decision to use chemotherapy must be individualized according to several factors, including patient preference, toxicity, survival benefit, quality of life, and cost of treatment.52,54,55

In a large randomized trial comparing 4 chemotherapy regimens for advanced non-small cell lung cancer, median survival (8.1 versus 7.8 months) and response rate (22 versus 21%) were similar for patients receiving gemcitabine and cisplatin versus paclitaxel and cisplatin.68 Although median time to progression of disease was longer in patients receiving gemcitabine and cisplatin (4.2 months) compared with paclitaxel and cisplatin (3.4 months), patients receiving the gemcitabine-containing regimen were more likely to experience hematologic toxicity (thrombocytopenia or anemia) or renal toxicity.68 A higher percentage of patients receiving gemcitabine and cisplatin withdrew from the study because of complications of therapy compared with those receiving paclitaxel and cisplatin (27 versus 15%).68

The current indication for gemcitabine in combination with cisplatin for the treatment of advanced non-small cell lung cancer is based principally on data from 2 randomized clinical studies involving a total of 657 patients.1,27,28 In a multicenter study, 522 patients with previously untreated, inoperable stage IIIA, IIIB, or IV non-small cell lung cancer were randomized to receive gemcitabine (1 g/m2 IV on days 1, 8, and 15) and cisplatin (100 mg/m2 IV on day 1) or cisplatin alone (100 mg/m2 IV on day 1) on a 28-day cycle.1,27 Characteristics of the patients on the 2 study arms were similar except for tumor histology, with more patients receiving cisplatin alone having adenocarcinoma (48 versus 37%).1 Patients receiving combination therapy with gemcitabine and cisplatin had a longer median survival time (9 versus 7.6 months), a longer median time to disease progression (5.2 versus 3.7 months), and a higher objective response rate (26 versus 10%) than patients receiving cisplatin alone.1 Duration of response and quality of life (assessed using the FACT-L, a scale incorporating physical, social, emotional, and functional well-being as well as lung cancer symptoms) were similar for the 2 study groups.1 Combined therapy with gemcitabine and cisplatin was associated with greater toxicity, particularly myelosuppression, compared with cisplatin monotherapy, and dose adjustments were required in 90% of patients receiving gemcitabine and cisplatin compared with 16% of patients receiving cisplatin alone.1

In a second multicenter, randomized study in 135 patients with stage IIIB or IV non-small cell lung cancer, patients were treated on 21-day cycles with cisplatin (100 mg/m2 IV on day 1) and either gemcitabine (1.25 g/m2 IV on days 1 and 8) or etoposide (100 mg/m2 IV on days 1, 2, and 3).1,28 Median survival (8.7 versus 7 months) and quality of life (using the EORTC QLQ-C30 and LC13, which evaluate physical and psychologic functioning and symptoms related to lung cancer and its treatment) were similar in patients receiving gemcitabine/cisplatin or etoposide/cisplatin, respectively.1 A longer median time to disease progression (5 versus 4.1 months) and a higher objective response rate (33 versus 14%) were observed in patients receiving gemcitabine and cisplatin compared with those receiving etoposide and cisplatin.1 Thrombocytopenia (grade 3 or 4) was more frequent in patients receiving the gemcitabine-containing regimen than in those receiving the etoposide-containing regimen; although the incidence of grade 4 neutropenia was lower in patients receiving gemcitabine with cisplatin versus etoposide with cisplatin, the need for dose reductions or omission of scheduled doses for gemcitabine in twice as many patients as needed for etoposide may have contributed to this difference.1

The use of gemcitabine in combination with other antineoplastic agents† for the treatment of non-small cell lung cancer is being investigated.69 In a randomized trial, patients with stage IIIB or IV non-small cell lung cancer receiving gemcitabine and docetaxel had similar response rates, median survival, and 1- or 2-year survival rates compared with those receiving cisplatin and docetaxel.69 Further study is needed to evaluate the role of platinum- and non-platinum-containing chemotherapy in the treatment of advanced non-small cell lung cancer.54

Monotherapy

Gemcitabine is an active agent in non-small cell lung cancer.36,37,38,49,50,51,54 In nonrandomized phase 2 studies of patients with advanced non-small cell lung cancer who had not received prior chemotherapy, objective response rates of approximately 20% (0-3% complete responses, 17-20% partial responses) have been observed with gemcitabine alone.36,37,38,50,51 In these studies, median duration of response ranged from 3.6-12.7 months, and median survival ranged from 7-9 months.36,37,38,50,51 Responses to gemcitabine also have been observed in patients with relapsed or refractory advanced non-small cell lung cancer who previously were treated with platinum-containing chemotherapy regimens.41 Gemcitabine therapy is well tolerated; because of the lower incidence of myelosuppression associated with its use compared with other agents used in the treatment of non-small cell lung cancer, the drug is particularly suited for use in combination chemotherapy regimens.36,37,38,50,51 Response rates do not appear to be significantly affected by a there appears to be similar efficacy and no difference in adverse effects in patients 70 years of age or older versus younger patients receiving gemcitabine alone for advanced non-small cell lung cancer.42,43,56 Noncomparative studies suggest that patients with advanced non-small cell lung cancer receiving gemcitabine experience relief of symptoms (including cough, hemoptysis, chest pain, dyspnea, and anorexia) and improvement in performance status.36,38,42,44,58

In 2 randomized phase 2 studies in patients with inoperable, locally advanced or metastatic non-small cell lung cancer that was previously untreated with chemotherapy, similar efficacy but less toxicity (leukopenia, nausea and vomiting, alopecia) was observed in those receiving gemcitabine alone versus combination therapy with cisplatin and etoposide.39,40

Dosage and Other Considerations

Although optimum dosage regimens have not been established, gemcitabine dosages of 1 or 1.25 g/m2 administered by 30-minute IV infusion once weekly for 3 weeks followed by 1 week of rest have been used most commonly in patients receiving gemcitabine as monotherapy for advanced non-small cell lung cancer.36,37,38,41,42,44,50,51 Various dosage schedules have been studied for the combination of gemcitabine with cisplatin for the treatment of advanced non-small cell lung cancer;27,28,29,30,31,32,33,34,53 gemcitabine dosages of 1 g/m2 administered once weekly for 3 weeks on a 4-week cycle or 1.25 g/m2 administered once weekly for 2 weeks on a 3-week cycle have been used in large randomized trials1,27,28 (see Dosage and Administration: Dosage); gemcitabine doses of 1-1.5 g/m2 have been used in combination with cisplatin in phase 2 studies.29,30,31,32,33,34,53 Other dosage schedules for gemcitabine (e.g., higher doses, lower doses administered over longer infusion periods) are being investigated in patients with advanced non-small cell lung cancer.46,47,48

Further study is needed to define the role of gemcitabine used alone or in combination therapy for the treatment of advanced non-small cell lung cancer.49,58 No single chemotherapy regimen currently can be recommended as superior in the treatment of non-small cell lung cancer.35,54,55 Various chemotherapy regimens used alone or in combination with other treatment modalities, such as radiation therapy, are continually being evaluated for the treatment of advanced non-small cell lung cancer.49,54,55 Because current treatment is not satisfactory for almost all patients with non-small cell lung cancer except selected patients with early-stage, resectable disease, all patients may be considered for enrollment in clinical trials at the time of diagnosis.54

Bladder Cancer !!navigator!!

Gemcitabine is an active agent that is used alone22,23,24 or in combination therapy5,59 for the treatment of advanced or metastatic bladder cancer†. Objective responses to gemcitabine have been observed in patients with metastatic bladder cancer that did not respond to previous treatment with cisplatin-based regimens, including some patients with hepatic metastases.24,25

Gemcitabine is used in combination with cisplatin as an alternative to M-VAC (i.e., cisplatin, methotrexate, and vinblastine with doxorubicin) for the treatment of advanced or metastatic bladder cancer.59,60 In a large randomized trial of patients receiving either gemcitabine (1 g/m2 over 30-60 minutes on days 1, 8, and 15) and cisplatin (70 mg/m2 on day 2) or M-VAC for the treatment of advanced or metastatic bladder cancer, overall median survival (13.8 versus 14.8 months, respectively), median time to progressive disease (7.4 months for each regimen), and response rates (44 versus 38%, respectively, using intent-to-treat analysis) were similar.59 Prophylactic hematopoietic agents (growth factors) were not administered to either group; grade 3 or 4 anemia or grade 3 or 4 thrombocytopenia were observed more often in patients receiving gemcitabine and cisplatin whereas grade 3 or 4 neutropenia, neutropenic sepsis, grade 3 or 4 mucositis, and alopecia occurred more frequently in patients receiving M-VAC.59

Gemcitabine also is used as a single agent for the treatment of advanced or metastatic bladder cancer.22,23 In a phase 2 study, gemcitabine 1.25 g/m2 was administered IV once weekly for 3 weeks every 4 weeks in patients with advanced bladder cancer that did not respond to previous treatment with cisplatin-based chemotherapy.22 Among 25 evaluable patients, an overall response rate of 28% (12% complete responses, 16% partial responses) was reported, and symptomatic improvements in hematuria, dysuria, cystitis, and polyuria were observed.22 In two other phase 2 studies, IV gemcitabine 1.2 g/m2 was administered once weekly for 3 weeks every 4 weeks in previously untreated patients with advanced or metastatic bladder cancer.23,26 Among 76 evaluable patients, overall response rates of 24-29% (8-11% complete responses, 16-18% partial responses) were observed.23,26 Gemcitabine appears to be well-tolerated in most patients with only mild toxicity.22,23,24,26

Further study is needed to define the precise role of gemcitabine in the treatment of advanced or metastatic bladder cancer, particularly in combination regimens.23,24,26

Biliary Tract Cancer !!navigator!!

Gemcitabine has been used in combination with cisplatin for the treatment of unresectable locally advanced or metastatic biliary tract cancer† (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer), including unresectable recurrent disease following surgical resection.76,78

Evidence concerning efficacy of chemotherapy regimens in the treatment of advanced biliary tract cancer is derived largely from small, nonrandomized, clinical studies and retrospective analyses; few large, randomized, controlled clinical trials have been conducted.76,77,80 Experts state that, in patients with biliary tract adenocarcinoma (the most common type of biliary tract cancer), chemotherapy can be recommended in individuals with unresectable locally advanced or metastatic disease and in those with recurrent disease following surgical resection,77 since there is some evidence from a randomized study in patients with unresectable pancreatic or biliary tract cancer indicating that use of chemotherapy for the treatment of unresectable biliary tract cancer is associated with prolonged survival and improved quality of life.77,79 Chemotherapy is recommended in such individuals with good performance status (ECOG performance status of 0 or 1).77 However, in patients with poor performance status (ECOG performance status of 2 or 3) or insufficient biliary decompression, the benefits of chemotherapy are limited and use of alternative therapy for palliation of associated symptoms (e.g., pain) and improvement in quality of life is recommended.77 In one retrospective analysis comparing chemotherapy with best supportive care in patients with advanced gallbladder cancer, a survival benefit was observed in patients with good performance status but not in those with poor performance status.77,81

In a multicenter, randomized, phase 3 trial (Advanced Biliary Cancer [ABC]-02), 410 patients with unresectable locally advanced or metastatic biliary tract carcinoma, including unresectable recurrent disease following surgical resection, were randomized to receive either combination therapy with gemcitabine (1 g/m2 administered by IV infusion over 30 minutes on days 1 and 8) and cisplatin (25 mg/m2 administered by IV infusion over 1 hour on days 1 and 8) on a 21-day cycle or gemcitabine alone (1 g/m2 administered by IV infusion over 30 minutes on days 1, 8, and 15) on a 28-day cycle.76,78 Patients without evidence of disease progression at 12 weeks could continue to receive their assigned regimen for an additional 12 weeks.76 Patients enrolled in the study generally had good baseline performance status (ECOG score of 0 or 1 in 88% of patients, score of 2 in 12%).76 Patients who had received prior systemic chemotherapy for locally advanced or metastatic biliary tract carcinoma (other than low-dose radiosensitizing chemotherapy given in conjunction with radiotherapy) were excluded from the study.78 At a median follow-up of 8.2 months, patients who received combination therapy with gemcitabine and cisplatin had longer median overall (11.7 versus 8.1 months) and progression-free (8 versus 5 months) survival, a higher 6-month progression-free survival rate (59.3 versus 42.5%), and higher rates of tumor control (complete or partial responses or stable disease) (81.4 versus 71.8%) compared with patients who received gemcitabine alone.76 Only one patient in each treatment group achieved a complete response.76 Grade 3 or 4 hematologic toxicity (most commonly neutropenia [25.3 versus 16.6%]) occurred more frequently in patients receiving combination therapy with gemcitabine and cisplatin, whereas grade 3 or 4 abnormalities in liver function (27.1 versus 16.7%), including elevations in serum ALT (SGPT) concentrations, occurred more frequently in patients receiving gemcitabine alone.76 Grade 3 or 4 infection occurred with similar frequency in both groups.76 Based on current evidence, combination therapy with gemcitabine and cisplatin is recommended (accepted) for use in the treatment of unresectable locally advanced or metastatic biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer), including unresectable recurrent disease following surgical resection, in patients with good performance status (ECOG performance status of 0 or 1).82

Dosage and Administration ⬆ ⬇

[Section Outline]

Reconstitution and Administration !!navigator!!

Gemcitabine hydrochloride is administered by IV infusion.1,11,57 The manufacturer states that the drug is for IV use only.1

Vials labeled as containing 200 mg or 1 g of gemcitabine should be reconstituted by adding 5 or 25 mL, respectively, of 0.9% sodium chloride injection without preservatives and shaking to dissolve.1 The resultant solutions have a gemcitabine concentration of 38 mg/mL, which accounts for the displacement volume of lyophilized powder (0.26 or 1.3 mL for vials labeled as containing 200 mg or 1 g, respectively).1,3,21 Smaller volumes should not be used for reconstitution since gemcitabine concentrations greater than 38 mg/mL may exceed the solubility of the drug and result in incomplete dissolution.1,3 The total volume upon reconstitution for vials labeled as containing 200 mg or 1 g is about 5.26 or 26.3 mL, respectively, and complete withdrawal of contents of the vials will provide 200 mg or 1 g, respectively.1,3 The reconstituted solutions can be infused IV without further dilution or as solutions that have been further diluted in 0.9% sodium chloride injection to gemcitabine concentrations as low as 0.1 mg/mL.1

Reconstituted and diluted solutions of gemcitabine hydrochloride generally are infused IV over a period of 30 minutes; any unused portion after preparation of the appropriate dose should be discarded.1 Increased toxicity, including clinically important myelosuppression, was observed in clinical trials when gemcitabine was infused over periods exceeding 60 minutes.1,15,17 In a phase 1 study designed to assess maximally tolerated infusion rates, the risk of clinically important myelosuppression was particularly great with infusion periods of 4.5 hours (270 minutes) or longer.1 Because prolonged IV infusion of gemcitabine hydrochloride is associated with a prolonged half-life and increased toxicity, the manufacturer warns that the infusion time for the drug should not exceed 60 minutes.1 (See Description.)

Prior to administration, reconstituted and diluted solutions of gemcitabine hydrochloride should be inspected visually whenever solution and container permit.1 If discoloration or particulate matter is present, the solution should be discarded.1 When reconstituted and/or diluted as directed, gemcitabine hydrochloride solutions are stable for 24 hours at controlled room temperatures of 20-25°C.1 The solutions should not be refrigerated since crystallization may occur.1

Dosage !!navigator!!

Dosage of gemcitabine hydrochloride is expressed in terms of gemcitabine and must be individualized based on body surface area and patient tolerance and response.1

The manufacturer warns that gemcitabine should not be administered more frequently than once weekly since the risk of toxicity is increased with such dosing.1,16 In a phase 1 trial designed to assess the maximum tolerated dose on a schedule of 5 consecutive daily doses, patients developed intolerable hypotension and flu-like symptoms16,18 at gemcitabine dosages exceeding 10 mg/m2 daily; the incidence and severity of these effects were dose related.1,3 In other dose-ranging phase 1 trials using twice-weekly schedules, maximum tolerated gemcitabine doses were 65 mg/m2 when the drug was infused over 30 minutes and 150 mg/m2 when the drug was injected over 5 minutes; in these trials, dose-limiting toxicities included thrombocytopenia and flu-like symptoms, particularly asthenia.1,16

Ovarian Cancer

For the treatment of advanced ovarian cancer in women whose disease has relapsed at least 6 months following completion of platinum-based therapy, the manufacturer recommends a regimen of gemcitabine 1 g/m2 administered by 30-minute IV infusion on days 1 and 8 of a 21-day cycle; carboplatin (at a dose required to obtain an area under the plasma concentration-time curve [AUC] of 4 mg/mL per minute) should be administered IV on day 1 after gemcitabine administration.1

Patients should have an absolute granulocyte count of at least 1500/mm3 and a platelet count of at least 100,000/mm3 prior to each cycle.1 If necessary, dosage of gemcitabine should be reduced or withheld according to the degree of hematologic toxicity.1 (See Hematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.) For adjustment of carboplatin dosage according to the degree of hematologic toxicity, see Dosage and Administration: Dosage, in Carboplatin 10:00; the manufacturer's prescribing information also should be consulted.1 In case of severe (i.e., grade 3 or 4) nonhematologic toxicity other than nausea and vomiting, gemcitabine doses should be withheld or reduced.1 (See Nonhematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.)

Breast Cancer

For initial treatment of metastatic breast cancer in adults following failure of anthracycline-containing adjuvant chemotherapy or in whom such chemotherapy was contraindicated, the manufacturer recommends a regimen of gemcitabine 1.25 g/m2 administered by 30-minute IV infusion on days 1 and 8 of a 21-day cycle; paclitaxel 175 mg/m2 should be administered as a 3-hour IV infusion on day 1 before administration of gemcitabine.1

Patients should have an absolute granulocyte count of at least 1500/mm3 and a platelet count of at least 100,000/mm3 prior to each cycle.1 If necessary, dosage of gemcitabine should be reduced or withheld according to the degree of hematologic toxicity.1 In case of severe (i.e., grade 3 or 4) nonhematologic toxicity other than alopecia or nausea and vomiting, gemcitabine doses should be withheld or reduced.1 (See Dosage Modification for Toxicity and Contraindications for Continued Therapy under Dosage and Administration: Dosage.) For adjustment of paclitaxel dosage according to the degree of hematologic or nonhematologic toxicity, see Dosage Modification for Toxicity and Contraindications for Continued Therapy under Dosage and Administration: Dosage, in Paclitaxel 10:00; the manufacturer's prescribing information also should be consulted.1

Pancreatic Cancer

The usual dosage of gemcitabine currently recommended by the manufacturer for the treatment of locally advanced or metastatic pancreatic carcinoma, either as first-line therapy in chemotherapy-naive patients or as second-line therapy in those previously treated with fluorouracil, is 1 g/m2 once weekly.1,11,57 For the initial cycle, this dosage is repeated at weekly intervals as tolerated for up to 7 weeks, followed by a week of rest from treatment.1 If necessary during the course of the initial cycle, dosage should be reduced or withheld according to the degree of hematologic toxicity. (See Hematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.) Subsequent cycles consist of once-weekly administration for 3 consecutive weeks of the usual or escalated dosage (see Dosage Escalation under Dosage: Pancreatic Cancer, in Dosage and Administration), if tolerated, or at dosages reduced according to the degree of hematologic toxicity, followed by a week of rest from treatment.1 In clinical trials, patients with pancreatic cancer reportedly received an average of 3 cycles of gemcitabine therapy.3 Because clearance of gemcitabine is reduced in women and geriatric patients, dosage reductions, including withholding of doses in some cases, may be more likely in these populations;1 however, there currently is no evidence that unusual dosage adjustments (i.e., other than those recommended in general for hematologic toxicity) would be required.1 In clinical trials, women tolerated the drug more poorly than men, were less likely to progress to subsequent cycles, and were more likely to experience hematologic toxicity (i.e., neutropenia and thrombocytopenia).1,3

Dosage Escalation

Dosage escalation can be considered for patients with pancreatic cancer who successfully complete the initial 7-week or subsequent 3-week cycle of gemcitabine therapy at the full weekly dosage of 1 g/m2, provided nadirs of the absolute granulocyte and platelet counts exceed 1500 and 100,000/mm3, respectively, and nonhematologic toxicity exceeding a World Health Organization (WHO) grade of 1 is not present.1,11 In such patients, the dosage can be increased to 1.25 g/m2 weekly.1 If a complete 3-week course at a dosage of 1.25 g/m2 is tolerated (i.e., these hematologic parameters are met and there is no evidence of WHO grade 1 nonhematologic toxicity), dosage can be escalated further to 1.5 g/m2 weekly given in 3-week cycles.1

Non-small Cell Lung Cancer

The optimum dosage regimen for gemcitabine when used in combination with cisplatin for the treatment of advanced non-small cell lung cancer has not been established.1 For the initial treatment of patients with inoperable, locally advanced (stage IIIA or IIIB) or metastatic (stage IV) non-small cell lung cancer, gemcitabine used in combination with cisplatin may be administered on either a 4-week schedule or a 3-week schedule with doses specific to the selected dosage schedule.1 For patients receiving combination therapy with gemcitabine and cisplatin on the 4-week schedule , the manufacturer recommends a regimen of gemcitabine 1 g/m2 administered by 30-minute IV infusion on days 1, 8, and 15 of each 28-day cycle; cisplatin 100 mg/m2 should be administered IV on day 1 following completion of the gemcitabine infusion.1 For patients receiving combination therapy with gemcitabine and cisplatin on the 3-week schedule , the manufacturer recommends a regimen of gemcitabine 1.25 g/m2 administered by 30-minute IV infusion on days 1 and 8 of each 21-day cycle; cisplatin 100 mg/m2 should be administered IV on day 1 following completion of the gemcitabine infusion.1

If necessary, dosage of gemcitabine should be reduced or withheld according to the degree of hematologic toxicity.1 (See Hematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.) For adjustment of cisplatin dosage according to the degree of hematologic toxicity, see Cautions: Precautions and Contraindications, in Cisplatin 10:00; the manufacturer's prescribing information also should be consulted.1 In case of severe (i.e., grade 3 or 4) nonhematologic toxicity other than alopecia or nausea and vomiting, gemcitabine and cisplatin doses should be withheld or reduced.1 (See Nonhematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.) The manufacturer also recommends careful monitoring of serum concentrations of creatinine, potassium, calcium, and magnesium in patients receiving gemcitabine in combination with cisplatin.1 Appropriate administration, hydration, and dosage adjustment guidelines for cisplatin should be followed.1 (See Cisplatin 10:00.)

Biliary Tract Cancer

When gemcitabine has been used in combination with cisplatin for the treatment of unresectable locally advanced or metastatic biliary tract cancer† in adults, including treatment of unresectable recurrent disease following surgical resection, gemcitabine 1 g/m2 has been administered by 30-minute IV infusion on days 1 and 8 of each 21-day cycle, and cisplatin 25 mg/m2 has been administered by 1-hour IV infusion on days 1 and 8 prior to gemcitabine administration.76,78 Treatment has been continued for 24 weeks (8 cycles of therapy) in the absence of disease progression or unacceptable toxicity.76,78

Dosage Modification for Toxicity and Contraindications for Continued Therapy

Hematologic Toxicity

A complete blood cell count (CBC), including differential and platelets, should be performed prior to each dose of gemcitabine.1 If myelosuppression is detected, therapy should be modified or temporarily withheld according to the degree of hematologic toxicity.1

In patients receiving gemcitabine for the treatment of advanced ovarian cancer , the dosage of gemcitabine within a cycle of treatment should be adjusted according to the granulocyte and platelet counts obtained on day 8 of therapy.1 For patients with absolute granulocyte counts of at least 1500/mm3 and platelet counts of at least 100,000/mm3, no adjustment in dosage is necessary.1 For those with absolute granulocyte counts of 1000-1499/mm3 and/or platelet counts of 75,000-99,999/mm3, 50% of the full dose should be given.1 If the absolute granulocyte count is less than 1000/mm3 and/or the platelet count is less than 75,000/mm3, the dose should be withheld.1 The dosage of gemcitabine in combination with carboplatin for subsequent cycles should be adjusted according to observed toxicity.1 The dosage of gemcitabine in subsequent cycles should be reduced to 800 mg/m2 on days 1 and 8 if any of the following hematologic toxicities occur: absolute granulocyte counts of less than 500/mm3 for more than 5 days or less than 100/mm3 for more than 3 days, febrile neutropenia, platelet counts of less than 25,000/mm3, or cycle delay of more than one week due to toxicity.1 If any of these toxicities recur after the initial dosage reduction, gemcitabine should be administered on day 1 only at a dose of 800 mg/m2 for the subsequent cycle.1

In patients receiving gemcitabine for the treatment of metastatic breast cancer , the dosage of gemcitabine should be adjusted according to the granulocyte and platelet counts obtained on day 8 of therapy.1 For patients with absolute granulocyte counts of at least 1200/mm3 and platelet counts exceeding 75,000/mm3, no adjustment in dosage is necessary.1 For those with absolute granulocyte counts of 1000-1199/mm3 or platelet counts of 50,000-75,000/mm3, 75% of the full dose should be given.1 For those with absolute granulocyte counts of 700-999/mm3 and platelet counts of at least 50,000/mm3, 50% of the full dose should be given.1 If the absolute granulocyte count is less than 700/mm3 or the platelet count is less than 50,000/mm3, the dose should be withheld.1

In patients receiving gemcitabine for the treatment of locally advanced or metastatic pancreatic carcinoma or advanced non-small cell lung cancer with absolute granulocyte counts of at least 1000/mm3 and platelet counts of at least 100,000/mm3, no adjustment in dosage is necessary.1 For those with absolute granulocyte counts of 500-999/mm3 or platelet counts of 50,000-99,999/mm3, 75% of the full dose should be given weekly.1,3 If the absolute granulocyte count is less than 500/mm3 or the platelet count is less than 50,000/mm3, the weekly dose should be withheld1 until the counts exceed these levels.3

Nonhematologic Toxicity

The diagnosis of hemolytic-uremic syndrome should be considered and gemcitabine should be discontinued immediately in patients who develop anemia with evidence of microangiopathic hemolysis, elevation of serum bilirubin or LDH, reticulocytosis, and/or severe thrombocytopenia with or without evidence of renal failure (e.g., elevation of serum creatinine or BUN).1,70

Gemcitabine should be discontinued immediately and appropriate supportive care (e.g., diuretics, corticosteroids) provided promptly in patients who develop severe adverse pulmonary effects.1,70,71

In patients receiving gemcitabine for the treatment of advanced ovarian cancer who develop grade 3 or 4 nonhematologic toxicity other than nausea and vomiting, gemcitabine doses should be withheld or reduced by 50%.1

In patients receiving gemcitabine for the treatment of metastatic breast cancer who develop grade 3 or 4 nonhematologic toxicity other than alopecia or nausea and vomiting, gemcitabine doses should be withheld or reduced by 50%.1

In patients receiving gemcitabine in combination with cisplatin for the treatment of advanced non-small cell lung cancer who develop grade 3 or 4 nonhematologic toxicity other than alopecia or nausea and vomiting, gemcitabine and cisplatin doses should be withheld or reduced by 50%.1

Special Populations !!navigator!!

The manufacturer states that there are insufficient data to recommend a dosage of gemcitabine in patients with renal or hepatic impairment.1 (See Adequate Patient Evaluation and Monitoring under Warnings/Precautions: General Precautions, in Cautions and see Hepatic Impairment and also see Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Cautions ⬆ ⬇

[Section Outline]

Contraindications !!navigator!!

Known hypersensitivity to gemcitabine or any ingredient in the formulation.1

Warnings/Precautions !!navigator!!

Warnings

IV Administration

Prolonged IV infusion of gemcitabine (i.e., over periods exceeding 60 minutes) and administration more frequent than once weekly may be associated with increased toxicity (e.g., myelosuppression).1 (See Dosage and Administration: Reconstitution and Administration.)

Hematologic Effects

The dose-limiting toxicity of gemcitabine is myelosuppression, including leukopenia, anemia, and thrombocytopenia.1 Patients receiving the drug may require red blood cell transfusions or, less frequently, platelet transfusions.1 Patients should be monitored for myelosuppression during therapy.1 A complete blood cell count (CBC), including differential and platelets, should be performed prior to each dose; dosage should be modified accordingly.1 (See Hematologic Toxicity under Dosage: Dosage Modification for Toxicity and Contraindications for Continued Therapy, in Dosage and Administration.)

Pulmonary Effects

Severe and sometimes fatal adverse pulmonary effects, including pulmonary edema, interstitial pneumonitis, pulmonary fibrosis, and adult respiratory distress syndrome (ARDS), have been reported in patients receiving one or more doses of gemcitabine; the drug should be discontinued immediately and appropriate supportive care (e.g., diuretics, corticosteroids) provided promptly in patients developing such effects.1,70,71 Onset of pulmonary symptoms has occurred up to 2 weeks following administration of the last dose of gemcitabine, and in rare instances, respiratory failure and death have occurred despite discontinuance of gemcitabine therapy.1 Dyspnea, unrelated to underlying disease and occasionally accompanied by bronchospasm, has been reported in patients receiving gemcitabine.1 Dose-limiting pulmonary toxicity, including esophagitis, pulmonary fibrosis, and pneumonitis, occurred in patients receiving gemcitabine and concurrent thoracic radiation therapy for non-small cell lung cancer.72 In addition, fatal pulmonary veno-occlusive disease has been reported in a patient who developed progressive dyspnea during gemcitabine therapy.67

Renal Effects

Hemolytic-uremic syndrome and/or renal failure have been reported in patients receiving one or more doses of gemcitabine.1 In rare cases, renal failure leading to death or requiring dialysis has occurred despite discontinuance of gemcitabine therapy.1 Cases of renal failure leading to death typically were caused by hemolytic-uremic syndrome.1 The diagnosis of hemolytic-uremic syndrome should be considered and gemcitabine should be discontinued immediately in patients who develop anemia with evidence of microangiopathic hemolysis, elevation of serum bilirubin or LDH, reticulocytosis, severe thrombocytopenia and/or evidence of renal failure (e.g., elevation of serum creatinine or BUN).1,70

Hepatic Effects

Serious hepatotoxicity, including hepatic failure and death, has been reported rarely in patients receiving gemcitabine alone or in combination with other potentially hepatotoxic drugs.1 In clinical studies, gemcitabine was associated with transient elevations in serum transaminases; however, there was no evidence of increasing hepatotoxicity with either longer duration of exposure to gemcitabine or with greater total cumulative dose.1 Elevated liver function test results, including increased concentrations of AST, ALT, γ-glutamyltransferase (GGT, γ-glutamyltranspeptidase, GGTP), alkaline phosphatase, and bilirubin, have been reported rarely during postmarketing surveillance.1

Fetal/Neonatal Morbidity and Mortality

Gemcitabine may cause fetal harm; teratogenicity and embryolethality have been demonstrated in animals.1 There are no studies to date in humans.1 If gemcitabine is used during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard.1

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions have been reported rarely during postmarketing surveillance in patients receiving gemcitabine.1

General Precautions

Adequate Patient Evaluation and Monitoring

Gemcitabine should be used under the supervision of a qualified clinician experienced in therapy with antineoplastic agents.1 Most adverse effects of the drug are reversible and do not require discontinuance of gemcitabine therapy, although withholding doses or reducing dosage may be necessary.1 (See Dosage Modification for Toxicity and Contraindications for Continued Therapy under Dosage and Administration: Dosage.)

Renal and hepatic function should be assessed prior to and periodically during gemcitabine therapy.1 A complete blood cell count, including differential and platelets, should be performed prior to each dose.1

Cardiovascular Effects

Cardiovascular toxicity, including congestive heart failure, myocardial infarction, and arrhythmias (mainly supraventricular), has been reported rarely during postmarketing surveillance in patients receiving gemcitabine.1 Vasculitis and gangrene also have been reported rarely in patients receiving the drug.1

Specific Populations

Pregnancy

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.) (See Users Guide.)

Lactation

It is not known whether gemcitabine is distributed into milk.1 The manufacturer states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman and the potential risk to nursing infants..1

Pediatric Use

Efficacy of gemcitabine has not been established in children younger than 18 years of age.1,3 In a phase 1 study in pediatric patients with refractory leukemia†, the maximum tolerated dosage of gemcitabine was 10 mg/m2 per minute for 6 hours (360 minutes) 3 times weekly, followed by 1 week of rest.1 When gemcitabine was administered at this dosage in a phase 2 study in patients with relapsed acute lymphoblastic leukemia† or acute myelogenous leukemia†, no clinically important activity was observed.1 Adverse effects reported in these studies were similar to those reported in adults and included bone marrow suppression, febrile neutropenia, increased serum transaminases, nausea, and rash/desquamation.1

Geriatric Use

Because gemcitabine clearance is reduced and half-life is increased in geriatric patients, dosage reductions, including withholding of doses in some cases, may be more likely in this population;1 however, there currently is no evidence that unusual dosage adjustments (i.e., other than those recommended in general for hematologic and nonhematologic toxicity) would be required.1 Information derived from the safety database for gemcitabine monotherapy indicates that the frequency of adverse effects in patients older than 65 years of age is similar to that in younger adults; however, severe (grade 3/4) thrombocytopenia has occurred more frequently in geriatric patients.1 In the clinical study of gemcitabine given in combination with carboplatin for recurrent ovarian cancer, no overall differences in efficacy or safety were observed between geriatric and younger patients; however, grade 3/4 neutropenia occurred more frequently in geriatric patients 65 years of age or older.1

Hepatic Impairment

Gemcitabine should be used with caution in patients with hepatic impairment.1 The effects of substantial hepatic insufficiency on the disposition of the drug have not been established.1 Use of gemcitabine in patients with current liver metastases or a history of hepatitis, alcoholism, or cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.1 (See Dosage and Administration: Special Populations and see Adequate Patient Evaluation and Monitoring under Warnings/Precautions: General Precautions, in Cautions.)

Renal Impairment

Gemcitabine should be used with caution in patients with renal impairment.1 The effects of substantial renal insufficiency on the disposition of the drug have not been established.1 (See Dosage and Administration: Special Populations and see Adequate Patient Evaluation and Monitoring under Warnings/Precautions: General Precautions, in Cautions.)

Women

Because gemcitabine clearance is reduced and half-life is increased in women, dosage reductions, including withholding of doses in some cases, may be more likely in this population;1 however, there currently is no evidence that unusual dosage adjustments (i.e., other than those recommended in general for hematologic and nonhematologic toxicity) would be required.1 In clinical studies with gemcitabine therapy, women, especially older women, were more likely not to proceed to the next cycle and more likely to experience World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia.1,3

Common Adverse Effects !!navigator!!

Adverse effects reported in 10% or more of patients receiving gemcitabine monotherapy include myelosuppression (i.e., anemia, leukopenia, neutropenia, thrombocytopenia), proteinuria, hematuria, increased BUN, nausea, vomiting, pain, fever, rash, pruritus, dyspnea, constipation, diarrhea, hemorrhage, peripheral edema, edema, flu-like symptoms, infection, alopecia, stomatitis, somnolence, paresthesias, and increased serum AST, ALT, alkaline phosphatase, and bilirubin concentrations.1

Drug Interactions ⬆ ⬇

[Section Outline]

No formal drug interaction studies have been performed to date.1

Antineoplastic Agents !!navigator!!

Based on data from patients with metastatic breast cancer, concomitant use of gemcitabine and paclitaxel appears to have minimal or no effect on the pharmacokinetics (i.e., clearance, half-life) of either drug.1

Based on data from patients with non-small cell lung cancer, concomitant use of gemcitabine and carboplatin does not appear to alter the pharmacokinetics of either drug compared with use of each drug alone.1

Radiation Therapy !!navigator!!

A pattern of tissue injury usually associated with radiation toxicity has been reported in association with concurrent and nonconcurrent use of gemcitabine and radiation therapy.1 Radiosensitizing activity of gemcitabine was observed in preclinical and clinical studies when the drug was administered with or within 7 days of radiation therapy (i.e., concurrent therapy).1 Gemcitabine has been associated with radiation recall reactions, but administration more than 7 days before or after radiation therapy (i.e., nonconcurrent therapy) does not otherwise appear to enhance toxicity.1 Available data suggest that gemcitabine therapy may be initiated once the acute effects of radiation therapy have resolved, or at least one week following radiation therapy.1

Toxicity in patients receiving combined modality treatment is dependent on many factors, including doses of gemcitabine and radiation, frequency of gemcitabine administration, radiotherapy planning technique, and target tissue and volume.1 In one study in patients with non-small cell lung cancer who received gemcitabine therapy (dose of 1 g/m2) and therapeutic thoracic radiation concurrently for up to 6 consecutive weeks, substantial toxicity (manifested as severe and potentially life-threatening mucositis, especially esophagitis and pneumonitis) was observed, particularly in those receiving large volumes of radiotherapy.1 Subsequent studies have suggested that toxicity is predictable and less severe when lower doses of gemcitabine are administered concurrently with radiation therapy; however, the optimal regimen for safe administration of gemcitabine with therapeutic dosages of radiation has not been established for all tumor types.1

Other Information ⬆ ⬇

Description

Gemcitabine hydrochloride, a synthetic pyrimidine nucleoside, is an antineoplastic agent.1,2,4 The nucleoside analog consists of the pyrimidine base difluorocytidine, and the sugar moiety deoxyribose.4

Like most antimetabolite antineoplastic agents, gemcitabine is cell-cycle specific, acting principally in the S phase of the cell cycle; the drug also may cause cellular arrest at the G1—S border.1 The cytotoxic activity of gemcitabine (2'-deoxy-2',2'-difluorocytidine) depends on intracellular conversion to its 5'-diphosphate and -triphosphate metabolites; thus, deoxydifluorocytidine-5'-diphosphate (dFdCDP, gemcitabine diphosphate) and -triphosphate (dFdCTP, gemcitabine triphosphate) and not unchanged gemcitabine are the pharmacologically active forms of the drug.1,2,4,19,58 Gemcitabine is phosphorylated by deoxycytidine kinase to gemcitabine monophosphate, which subsequently is phosphorylated to the corresponding diphosphate and triphosphate nucleosides, presumably by deoxycytidylate kinase and nucleoside diphosphate kinase, respectively.1,3,4,19,20,58 The cytotoxic effect of gemcitabine is attributed to the combined actions of its diphosphate and triphosphate nucleosides, which lead to inhibition of DNA synthesis.1,2,4,19,20,58

Gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for catalyzing the formation of deoxynucleoside triphosphates needed in DNA synthesis.1,2,4,58 By inhibiting this reductase, gemcitabine diphosphate interferes with subsequent de novo nucleotide production.1,2,4,58 Gemcitabine triphosphate inhibits DNA synthesis by competing with the physiologic substrate, deoxycytidine triphosphate, for DNA polymerase and incorporation into DNA.1,2,4,58 The reduction in intracellular concentrations of deoxycytidine triphosphate induced by gemcitabine diphosphate actually enhances the incorporation of gemcitabine triphosphate into DNA, a mechanism referred to as “self-potentiation.”1,3,58 Following incorporation of gemcitabine triphosphate into the DNA chain, a single additional nucleotide, a normal base pair, is added and DNA synthesis is terminated, resulting in apoptosis (programmed cell death).1,2,4,58 DNA polymerase ε is unable to recognize the abnormal (gemcitabine) nucleotide and repair the DNA strand as a result of masking by the terminal normal base pair nucleotide (masked chain termination).1,2,3,4,58 This inability to recognize and excise the abnormal nucleotide results in a prolonged intracellular half-life of gemcitabine compared with other nucleoside analogs such as cytarabine and is thought to contribute to gemcitabine's expanded spectrum of antineoplastic activity relative to such agents.4,58 In CEM T lymphoblastoid cells, gemcitabine induces internucleosomal DNA fragmentation, which is characteristic of programmed cell death.1

Following infusion of a single 1-g/m2 dose over 30 minutes, gemcitabine is excreted principally in urine as unchanged drug (less than 10%) and as the inactive metabolite, 2'-deoxy-2',2'-difluorouridine (dFdU).1 The inactive metabolite, dFdU, does not appear to accumulate with weekly dosing; however, it is excreted by the kidneys and may accumulate in patients with decreased renal function.1 The inactive metabolite also is found in plasma.1 The active metabolite, deoxydifluorocytidine-5'-triphosphate (dFdCTP, gemcitabine triphosphate), can be extracted from peripheral blood mononuclear cells.1 Volume of distribution and half-life of gemcitabine increase with longer infusion times.1 The half-life of gemcitabine ranges from 42-94 minutes and 4.1-10.6 hours following short and long infusions, respectively, depending on the patient's age and gender.1 Clearance is reduced and half-life increased in women and geriatric patients.1 Following a short (less than 70 minutes) infusion, the half-life of gemcitabine is approximately 42, 48, 61, and 79 minutes for men 29, 45, 65, and 79 years of age, respectively, and 49, 57, 73, and 94 minutes for women 29, 45, 65, and 79 years of age, respectively.1 The terminal phase half-life for the active metabolite, gemcitabine triphosphate, in mononuclear cells ranges from 1.7-19.4 hours.1

For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Advice to Patients

Risk of myelosuppression.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Gemcitabine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

200 mg (of gemcitabine)

Gemzar®

Lilly

1 g (of gemcitabine)

Gemzar®

Lilly

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions February 28, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

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3. Eli Lilly and Company, Indianapolis, IN: Personal communication.

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