Version July 2025
Note: Details concerning dosing in combination regimens should also be consulted. Prolongation of the infusion time >60 minutes and administration more frequently than once weekly have been shown to increase toxicity. Gemcitabine is associated with a low emetic potential risk; antiemetics are recommended to prevent nausea and vomiting (Ref). Infugem premix bags have been discontinued in the United States for >1 year.
Germ cell tumor, refractory: Limited data available: Adolescents ≥16 years: IV: 1,200 mg/m2/dose over 30 minutes on days 1, 8, and 15; repeat cycle every 28 days for up to 6 cycles (Ref).
Hodgkin lymphoma, relapsed or refractory: Limited data available; dosing regimens variable:
Gemcitabine in combination with brentuximab: Children and Adolescents: IV: 1,000 mg/m2/dose over 100 minutes on days 1 and 8 (in combination with brentuximab); repeat cycle every 21 days; in the trial, the inclusion criteria had no minimum age and the youngest patient was 5 years of age (Ref).
Gemcitabine in combination with vinorelbine:
Children ≥10 years and Adolescents: IV: 1,000 mg/m2/dose over 100 minutes on days 1 and 8 (in combination with vinorelbine); repeat cycle every 21 days (Ref).
Adolescents ≥17 years: IV: 1,000 mg/m2/dose over 60 minutes on days 1, 8, and 15 (in combination with vinorelbine); repeat cycle every 28 days (Ref). Alternatively, 800 mg/m2/dose on days 1 and 4 (in combination with ifosfamide and vinorelbine); repeat cycle every 21 days (Ref).
Sarcomas, refractory or relapsed (including Ewing sarcoma, osteosarcoma): Limited data available: Children ≥3 years and Adolescents: IV: 675 or 1,000 mg/m2/dose over 90 minutes on days 1 and 8 (in combination with docetaxel); repeat cycle every 21 days (Ref). Alternatively, 1,000 mg/m2/dose over 30 minutes on days 1 and 8 (in combination with oxaliplatin and irinotecan); repeat cycle every 28 days (Ref).
Solid tumors, relapsed/refractory: Limited data available: Children ≥1 year and Adolescents: IV: 1,000 mg/m2/dose over 30 minutes on days 1 and 8 (in combination with oxaliplatin and irinotecan); repeat cycle every 28 days (Ref). Alternatively, 1,000 mg/m2/dose over 100 minutes on day 1 (in combination with oxaliplatin); repeat cycle every 14 days (Ref).
Note: Dosage reductions for toxicity (Ref): 800 mg/m2/dose over 80 minutes if grade 3/4 nonhematological toxicity, grade 4 neutropenia with documented infection or lasting >7 days, grade 3/4 thrombocytopenia lasting >7 days or requiring platelets during >7 days, or delay of next cycle ≥14 days; if necessary, dose could be reduced a second time to 600 mg/m2/dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.
Adult:
Nonhematologic toxicity (all indications):
Hold or decrease gemcitabine dose by 50% for the following: Severe (grade 3 or 4) nonhematologic toxicity until resolved (excludes nausea, vomiting, or alopecia [no dose modifications recommended]).
Permanently discontinue gemcitabine for any of the following: Unexplained dyspnea (or other evidence of severe pulmonary toxicity), severe hepatotoxicity, hemolytic uremic syndrome (HUS), capillary leak syndrome (CLS), posterior reversible encephalopathy syndrome (PRES).
Hematologic toxicity:
Breast cancer:
Day 1:
Absolute neutrophil count (ANC) ≥1,500/mm3 and platelet count ≥100,000/mm3: Administer 100% of full dose.
ANC <1,500/mm3 or platelet count <100,000/mm3: Hold dose.
Day 8:
ANC ≥1,200/mm3 and platelet count >75,000/mm3: Administer 100% of full dose.
ANC 1,000 to 1,199/mm3 or platelet count 50,000 to 75,000/mm3: Administer 75% of full dose.
ANC 700 to 999/mm3 and platelet count ≥50,000/mm3: Administer 50% of full dose.
ANC <700/mm3 or platelet count <50,000/mm3: Hold dose.
Non-small cell lung cancer (cisplatin dosage may also require adjustment):
ANC ≥1,000/mm3 and platelet count ≥100,000/mm3: Administer 100% of full dose.
ANC 500 to 999/mm3 or platelet count 50,000 to 99,999/mm3: Administer 75% of full dose.
ANC <500/mm3 or platelet count <50,000/mm3: Hold dose.
Ovarian cancer:
Day 1:
ANC ≥1,500/mm3 and platelet count ≥100,000/mm3: Administer 100% of full dose.
ANC <1,500/mm3 or platelet count <100,000/mm3: Delay treatment cycle.
Day 8:
ANC ≥1,500/mm3 and platelet count ≥100,000/mm3: Administer 100% of full dose.
ANC 1,000 to 1,499/mm3 or platelet count 75,000 to 99,999/mm3: Administer 50% of full dose.
ANC <1,000/mm3 or platelet count <75,000/mm3: Hold dose.
Hematologic toxicity in previous cycle (dosing adjustment for subsequent cycles):
Initial occurrence: ANC <500/mm3 for >5 days, ANC <100/mm3 for >3 days, febrile neutropenia, platelet count <25,000/mm3, or cycle delay >1 week due to toxicity: Permanently reduce gemcitabine to 800 mg/m2 on days 1 and 8.
Subsequent occurrence: ANC <500/mm3 for >5 days, ANC <100/mm3 for >3 days, neutropenic fever, platelet count <25,000/mm3, or cycle delay >1 week due to toxicity: Permanently reduce gemcitabine to 800 mg/m2 and administer on day 1 only.
Pancreatic cancer:
ANC ≥1,000/mm3 and platelet count ≥100,000/mm3: Administer 100% of full dose.
ANC 500 to 999/mm3 or platelet count 50,000 to 99,999/mm3: Administer 75% of full dose.
ANC <500/mm3 or platelet count <50,000/mm3: Hold dose.
(For additional information see "Gemcitabine: Drug information")
Dosage guidance:
Safety: Prolongation of the infusion duration >60 minutes and administration more frequently than once weekly have been shown to increase toxicity.
Dosage form information: If using premixed infusion bags, select the premixed bag(s) that allows for a variance of ≤5% of the BSA-based calculated dose; do not use premixed infusions bags for patients requiring a bag size of <1,200 mg/dose (select a different formulation). Infugem premix bags have been discontinued in the United States for >1 year.
Clinical considerations: Refer to the protocol or institutional guidance for additional details of off-label dosing.
Biliary tract cancer, adjuvant therapy (off-label use): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with capecitabine) for 4 cycles, followed by capecitabine in combination with concurrent radiotherapy (Ref).
Biliary tract cancer, advanced (off-label use):
In combination with cisplatin: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin); continue until disease progression or unacceptable toxicity or a maximum of 8 cycles (Ref).
In combination with cisplatin and durvalumab: IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with durvalumab and cisplatin) for up to 8 cycles, followed by durvalumab as a single agent until disease progression or unacceptable toxicity (Ref).
In combination with cisplatin and pembrolizumab: IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin [maximum 8 cycles] and pembrolizumab [maximum 35 cycles]) until disease progression or unacceptable toxicity (Ref).
In combination with capecitabine: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with capecitabine); continue until disease progression or unacceptable toxicity (Ref).
In combination with oxaliplatin: IV: 1,000 mg/m2 infused at 10 mg/m2/minute once every 2 weeks (in combination with oxaliplatin); continue until disease progression or unacceptable toxicity (Ref).
In combination with paclitaxel (protein bound): IV: 1,000 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (in combination with paclitaxel [protein-bound]); continue until disease progression or unacceptable toxicity (Ref).
Bladder cancer, non–muscle invasive, transitional cell, refractory (off-label use): Intravesicular instillation : 2,000 mg (in 100 mL NS; retain for 1 hour) twice weekly for 3 weeks; repeat cycle every 4 weeks for at least 2 cycles (Ref).
Breast cancer, metastatic: IV: 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with paclitaxel); continue until disease progression or unacceptable toxicity (Ref)
Off-label dosing/combinations:
Single-agent therapy: IV: 800 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (as a single agent); continue until disease progression or unacceptable toxicity; dose could be increased if the first cycle was tolerated (Ref).
In combination with carboplatin and pembrolizumab (triple-negative breast cancer): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with carboplatin and pembrolizumab [maximum 35 cycles]); continue chemotherapy until disease progression or unacceptable toxicity (Ref).
In combination with margetuximab (HER2- positive): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with margetuximab); continue until disease progression or unacceptable toxicity (Ref).
Cervical cancer, recurrent or persistent (off-label use): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) for up to 6 cycles; patients with a partial response who tolerated the regimen could continue (at discretion) beyond 6 cycles (Ref) or 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin); continue until disease progression, complete regression, or (for patients with stable disease) for 6 cycles (Ref) or 800 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (as a single-agent); continue until disease progression or unacceptable toxicity (Ref) or 800 mg/m2 on days 1 and 8 of a 28-day treatment cycle (in combination with cisplatin); continue until disease progression or unacceptable toxicity (Ref).
Head and neck cancer: nasopharyngeal, locally advanced, advanced, or metastatic (off-label use):
Locally advanced disease: Gemcitabine/cisplatin induction chemotherapy: IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) for 3 cycles followed by chemoradiation (Ref). A minimum of 2 cycles is recommended (Ref).
Adjuvant therapy for N2-3 disease: IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) for 3 cycles following concurrent chemoradiotherapy (Ref).
Metastatic or recurrent, locally advanced (first-line treatment): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin and toripalimab) until disease progression or unacceptable toxicity for up to a maximum of 6 combination cycles (whichever occurred first); followed by single-agent toripalimab until disease progression or unacceptable toxicity (Ref).
Advanced or metastatic disease: IV: 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (Ref) or 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with vinorelbine) (Ref).
Hodgkin lymphoma, relapsed or refractory (off-label use):
GVD regimen: IV: 1,000 mg/m2 (800 mg/m2 if post-transplant) over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with vinorelbine and doxorubicin [liposomal]) for 2 to 6 cycles (in the absence of disease progression or unacceptable toxicity) (Ref).
IGEV regimen: IV: 800 mg/m2 on days 1 and 4 of a 21-day treatment cycle (in combination with ifosfamide, mesna, vinorelbine, and prednisolone) for 4 cycles (Ref).
Mesothelioma, pleural (off-label use):
Single-agent therapy: IV: 1,250 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (as a single agent) for up to 10 cycles or until disease progression or unacceptable toxicity (Ref) or 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity (Ref).
In combination with cisplatin: IV: 1,000 mg/m2 over 30 minutes on days 1, 8 and 15 of a 28-day treatment cycle (in combination with cisplatin) for up to 6 cycles (Ref) or 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) for up to 6 cycles (Ref).
Non-Hodgkin lymphoma, relapsed or refractory (off-label use):
GDP-(R) regimen: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin, dexamethasone, ± rituximab); continue for 2 to 3 cycles followed by autologous hematopoietic cell transplant (HCT) or up to 6 cycles (in patients with response and are not candidates for autologous HCT) (Ref).
GemOx-R regimen: IV: 1,000 mg/m2 every 14 to 21 days (in combination with oxaliplatin and rituximab) for 4 to 8 cycles (Ref); some studies used a fixed dose rate infusion.
R-GCVP regimen: IV: 750 mg/m2 over 30 minutes (cycle 1; sequentially increase dose to 875 mg/m2 in cycle 2, followed by 1,000 mg/m2 in cycle 3 onward, as tolerated) on days 1 and 8 of a 21-day treatment cycle (in combination with rituximab, cyclophosphamide, vincristine, and prednisolone) for 6 cycles (Ref).
Non–small cell lung cancer, resectable (off-label):
Neoadjuvant treatment (squamous histology):
In combination with platinum and durvalumab: IV: 1,250 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin [or carboplatin if unable to receive cisplatin] and durvalumab) for 4 cycles followed by surgery and adjuvant durvalumab (as a single agent) (Ref).
In combination with cisplatin and nivolumab: IV: 1,000 or 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin and nivolumab) for up to 3 cycles (Ref).
In combination with cisplatin and pembrolizumab: IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin and pembrolizumab) for 4 cycles followed by definitive surgery within 20 weeks after the first cycle of the neoadjuvant phase and then adjuvant therapy with up to 39 weeks of pembrolizumab (as a single agent) beginning between 4 to 12 weeks following definitive surgery (Ref).
Non–small cell lung cancer, inoperable, locally advanced, or metastatic: IV: 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (in combination with cisplatin) for a maximum of 6 cycles (Ref) or 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) for a maximum of 6 cycles (Ref).
Off-label dosing/combinations:
In combination with durvalumab, tremelimumab, and a platinum (squamous histology): IV: 1,000 or 1,250 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin or carboplatin, durvalumab and tremelimumab) for 4 cycles, followed by tremelimumab (for 1 additional dose) and durvalumab; continue durvalumab until disease progression or unacceptable toxicity (Ref).
In combination with carboplatin: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with carboplatin) for up to 4 cycles (Ref) or 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (in combination with carboplatin) for up to 4 cycles (Ref).
In combination with docetaxel: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with docetaxel) for 8 cycles (Ref).
In combination with vinorelbine: IV: 900 to 1,000 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (in combination with vinorelbine) for 6 cycles (Ref).
Ovarian cancer, advanced: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with carboplatin) for 6 cycles (Ref).
Off-label dosing/combinations:
Single-agent therapy: IV: 1,000 mg/m2 over 30 to 60 minutes on days 1 and 8 of a 21-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref) or 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
In combination with carboplatin and bevacizumab (recurrent; platinum sensitive): IV: 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with carboplatin and bevacizumab) for 6 to 10 cycles, followed by bevacizumab (as a single agent) until disease progression or unacceptable toxicity (Ref).
Pancreatic cancer, potentially curable, adjuvant therapy (off-label use; alternative therapy): Note: American Society of Clinical Oncology guidelines for potentially curable pancreatic cancer recommend 6 months of adjuvant therapy if recovery is complete; while first-line therapy with another regimen is preferred, the gemcitabine/capecitabine regimen or single-agent gemcitabine therapy are options if toxicity/tolerance are concerns with the preferred regimen (Ref).
Combination regimen: IV: 1,000 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (in combination with capecitabine) for 6 cycles beginning within 12 weeks of resection (Ref).
Single-agent therapy: IV: 1,000 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle for 6 cycles (Ref).
Pancreatic cancer, locally advanced or metastatic: IV: 1,000 mg/m2 over 30 minutes once weekly for 7 weeks followed by 1 week rest (cycle 1), then administer on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Off-label dosing/combinations:
In combination with paclitaxel [protein bound]: IV: 1,000 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (in combination with paclitaxel [protein bound]); continue until disease progression or unacceptable toxicity (Ref).
In combination with cisplatin: IV: 1,000 mg/m2 over 30 minutes on days 1 and 15 of a 28-day treatment cycle (in combination with cisplatin) (median number of cycles: 4 [range: up to 20 cycles]) (Ref).
In combination with capecitabine: IV: 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (in combination with capecitabine); continue until disease progression or unacceptable toxicity (Ref).
In combination with erlotinib: IV: 1,000 mg/m2 over 30 minutes once weekly for 7 weeks followed by 1 week rest (cycle 1); then administer on days 1, 8, and 15 of a 28-day treatment cycle (in combination with erlotinib); continue until disease progression or unacceptable toxicity (Ref).
In combination with oxaliplatin: IV: 1,000 mg/m2 infused at 10 mg/m2/minute every 14 days (in combination with oxaliplatin); continue until disease progression or unacceptable toxicity (Ref).
Renal carcinoma, non-clear cell, metastatic (off-label use): IV: 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with either cisplatin or carboplatin); continue until disease progression or unacceptable toxicity for up to a maximum of 9 cycles (Ref).
Sarcoma (off-label use):
Ewing sarcoma, refractory: IV: 675 mg/m2 over 90 minutes on days 1 and 8 of a 21-day cycle (in combination with docetaxel) until disease progression or unacceptable toxicity (median number of cycles: 4 [range: 1 to 13 cycles]) (Ref).
Osteosarcoma, refractory: IV: 675 mg/m2 over 90 minutes on days 1 and 8 of a 21-day cycle (in combination with docetaxel) until disease progression or unacceptable toxicity (median number of cycles: 4 [range: 1 to 13 cycles]) (Ref) or 1,000 mg/m2 once weekly for 7 weeks followed by 1 week rest; followed by 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity (Ref).
Soft tissue sarcoma, advanced:
In combination with docetaxel: IV: 675 mg/m2 over 90 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with docetaxel) (median number of cycles: 5 [range: 1 to 8 cycles]) (Ref) or 900 mg/m2 over 90 minutes on days 1 and 8 of a 21-day cycle (in combination with docetaxel) for up to 8 cycles (Ref).
In combination with dacarbazine: IV: 1,800 mg/m2 over 180 minutes (at a rate of 10 mg/m2/minute) once every 2 weeks (in combination with dacarbazine) for up to 12 cycles (Ref).
In combination with vinorelbine: IV: 800 mg/m2 over 90 minutes on days 1 and 8 of a 21-day cycle (in combination with vinorelbine); continue until disease progression or unacceptable toxicity (Ref).
Small cell lung cancer, relapsed or refractory (off-label use): IV: 1,000 to 1,250 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (as a single agent); continue until disease progression or unacceptable toxicity (Ref).
Testicular cancer, refractory germ cell (off-label use):
In combination with oxaliplatin: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with oxaliplatin) for up to 6 cycles or for 2 cycles beyond the best response (Ref) or 1,250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with oxaliplatin) (median number of cycles: 3 [range: 1 to 6 cycles]) (Ref).
In combination with paclitaxel: IV: 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle for up to 6 cycles (in combination with paclitaxel) (Ref).
In combination with oxaliplatin and paclitaxel: IV: 800 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with oxaliplatin and paclitaxel) for a minimum of 2 cycles and for up to 8 cycles (Ref).
Thymoma and thymic carcinoma, advanced or metastatic, relapsed or refractory (later-line therapy) (off-label use): IV: 1,000 mg/m2 on days 1 and 8 every 3 weeks (as a single agent or in combination with capecitabine); continue until disease progression or unacceptable toxicity (Ref).
Unknown primary carcinoma (off-label use): IV: 1,250 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with cisplatin) (Ref) or 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle for up to 6 cycles (in combination with docetaxel) (Ref) or 1,000 mg/m2 on days 1 and 8 of a 21-day treatment cycle (in combination with irinotecan) for 4 to 6 cycles (Ref).
Urothelial carcinoma, locally advanced, unresectable, or metastatic (off-label use):
In combination with carboplatin: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with carboplatin); continue until disease progression or unacceptable toxicity (Ref).
In combination with cisplatin: IV: 1,000 mg/m2 over 30 to 60 minutes on days 1, 8, and 15 of a 28-day treatment cycle (in combination with cisplatin) for up to 6 cycles (Ref).
In combination with cisplatin and nivolumab: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with nivolumab and cisplatin) for up to 6 cycles, followed by nivolumab (as a single agent) until disease progression, unacceptable toxicity, or for up to 2 years (Ref).
PCG (gemcitabine, paclitaxel, cisplatin) regimen: IV: 1,000 mg/m2 over 30 minutes on days 1 and 8 of a 21-day treatment cycle (in combination with paclitaxel and cisplatin) for up to 6 cycles or until disease progression or unacceptable toxicity (Ref).
Uterine sarcoma, recurrent or metastatic (off-label use): IV: 900 mg/m2 over 90 minutes days 1 and 8 of a 21-day treatment cycle (in combination with docetaxel) until disease progression or unacceptable toxicity (Ref) or 1,000 mg/m2 over 30 minutes days 1, 8, and 15 of a 28-day treatment cycle (as a single agent) (median number of cycles: 2 [range: 1 to 13 cycles]) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Dosage adjustment prior to treatment initiation:
Altered kidney function:
CrCl ≥30 mL/minute: IV: No dosage adjustment necessary (Ref).
CrCl <30 mL/minute: IV: No dosage adjustment necessary. However, risk of hematologic toxicity may be increased in these patients, which may require gemcitabine dose modification (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Gemcitabine is metabolized intracellularly and then converted to dFdU; dFdU is dialyzable (~50% removal by single session (Ref)).
IV: No dosage adjustment necessary (Ref). Consider performing hemodialysis 6 to 12 hours after completing the gemcitabine infusion to limit the potential toxic effects of dFdU accumulation (Ref). Risk of hematologic toxicity may be increased in patients with severe kidney impairment, which may require gemcitabine dose modification (Ref).
Peritoneal dialysis: Extent of dialyzability unknown:
IV: No dosage adjustment necessary (Ref). Risk of hematologic toxicity may be increased in patients with severe kidney impairment, which may require gemcitabine dose modification (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions (eg, myelosuppression) due to drug accumulation is important.
IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, myelosuppression) due to drug accumulation is important.
IV: No dosage adjustment necessary (expert opinion). Consider performing PIRRT 6 to 12 hours after completing the gemcitabine infusion to limit the potential toxic effects of dFdU accumulation (Ref).
Dosage adjustment for kidney toxicity during treatment: Permanently discontinue if severe kidney toxicity or hemolytic uremic syndrome occur during gemcitabine treatment.
Hepatic impairment prior to treatment initiation:
There are no dosage adjustments provided in the manufacturer's labeling. The following adjustments have been reported:
Transaminases elevated (with normal bilirubin or total bilirubin <1.6 mg/dL): No dosage adjustment necessary (Ref).
Serum bilirubin >1.6 mg/dL: Use initial dose of 800 mg/m2; may escalate if tolerated (Ref).
Total bilirubin ≥1.6 mg/dL: May begin with 80% of the usual gemcitabine dose and increase the dose if tolerated or may consider initiating with full dose and careful active monitoring (Ref).
Acute hepatotoxicity during treatment: Permanently discontinue if severe hepatotoxicity occurs during gemcitabine treatment.
Edema is a relatively common adverse reaction of gemcitabine, thought to be related to increased vascular permeability, and potentially a reason for drug interruption or discontinuation. Rarely, systemic capillary leak syndrome (SCLS) may occur, including fatal cases. SCLS is described as a “sepsis-like” disorder characterized by rapid accumulation of diffuse edema, weight gain, noncardiogenic pulmonary edema, hypoalbuminemia, and hypotension and increased hematocrit secondary to decreased intravascular volume (Ref). Ultimately, hypoperfusion can lead to hypovolemic shock and end-organ damage. Furthermore, increased vascular permeability has been implicated as a potential cause or exacerbating factor for gemcitabine-related toxicity in the brain, lungs, and kidneys (Ref).
Mechanism: Not clearly established; may be due to endothelial dysfunction secondary to cytokine signaling; gemcitabine-treated patients have demonstrated increases in interleukin (IL)-2 and tumor necrosis factor (TNF)-α (Ref). Another proposed mechanism suggests cellular toxicity to the endothelium, likely a result of mitochondrial damage by active gemcitabine metabolites, leading to the creation of reactive oxygen species (Ref).
Onset: Varied; case reports of SCLS describe an acute onset of severe symptoms over the course of hours to a few days, but typically occurs more than 30 days after initiation of gemcitabine therapy (Ref).
Risk factors:
• Concurrent administration with other chemotherapy (carboplatin, oxaliplatin, taxanes) (Ref)
• Use of granulocyte colony stimulating factor (Ref)
• Omission of corticosteroids as antiemetic prophylaxis (Ref)
• Baseline peripheral edema or predisposition (poor nutritional status, deep vein thrombosis, retroperitoneal lymphadenopathy) (Ref)
Treatment with gemcitabine is associated with suppressed hematopoiesis, resulting in decreases in one or more blood cell lineages (anemia, neutropenia, or thrombocytopenia) (Ref). Myelosuppression is generally considered the dose-limiting toxicity for gemcitabine and is a common indication for dose modification. When gemcitabine is administered concurrently with other chemotherapy agents, higher incidences of anemia, neutropenia, and thrombocytopenia are observed, including grades 3 to 4. A fixed-dose infusion rate of 10 mg/m2/minute appears to increase hematologic toxicity compared to the standard 30-minute infusion (Ref); refer to the institutional guidance or protocol for additional details based on indication.
Mechanism: Dose-related; progenitor cells within the bone marrow are particularly susceptible to cellular cytotoxicity from chemotherapy agents due to the near constant DNA synthesis and replication required for hematopoiesis. Neutropenia and thrombocytopenia were the most common dose-limiting toxicities in early phase trials, likely due to the relatively short circulating half-life of these mature cells (Ref). Transient thrombocytosis has been reported in ~20% of patients in a phase II study, likely resulting in increased hematopoiesis in response to the interruption produced by gemcitabine administration (Ref).
Onset: Varied; neutrophil and platelet nadirs tend to occur within 7 to 10 days, respectively (Ref).
Risk factors:
• Higher doses (Ref)
• Longer infusion duration (>30 minutes) (Ref)
• More frequent administration (> weekly) (Ref)
• Concurrent administration with other chemotherapy
• Concurrent radiation therapy (Ref)
• Older age (Ref)
Transient increases in serum aminotransferases may occur. Serious hepatotoxicity, including hepatic failure and death, has been reported (Ref). The pattern of liver injury varies and may include mild asymptomatic transaminitis, cholestatic hepatitis, veno-occlusion (hepatic sinusoidal obstructive syndrome), and fulminant hepatic failure (Ref).
Mechanism: Non–dose-related (idiosyncratic); most likely related to direct hepatocellular injury, although there does not appear to be a dose-dependent relationship (Ref). Gemcitabine-induced liver injury may result in occlusion of terminal hepatic venules and sinusoidal congestion (veno-occlusive) or parenchymal necrosis and intracellular and intracanalicular cholestasis (cholestatic) (Ref).
Onset: Varied; transient elevations in serum aminotransferases usually occur at the time of the next dose (ie, 7 days after exposure). Cases of serious hepatoxicity are generally delayed (Ref).
Risk factors:
• Prior or concurrent hepatotoxic chemotherapy (Ref)
• Concurrent hepatotoxic medications
• Baseline hepatic impairment (Ref)
• Concurrent liver metastases (Ref)
• History of hepatitis B virus/hepatitis C virus infection (Ref)
Multiple delayed hypersensitivity reactions, ranging from a mild, maculopapular rash (also known as morbilliform drug eruption) to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and acute generalized exanthematous pustulosis (AGEP), have been reported (Ref). Maculopapular rash is usually self-limiting and localized to part of the trunk or extremities (Ref). Drug reaction with eosinophilia and systemic symptoms (DRESS) has also been reported; however, symptoms occurred on day 3 of gemcitabine administration and included mainly fever, rash, and relative eosinophilia. Given the short latency, this case may be a nonspecific delayed hypersensitivity reaction (Ref).
Mechanism: Maculopapular rash: Non–dose-related, unknown. Some patients can tolerate re-administration of gemcitabine, suggesting a nonimmunologic mechanism (Ref). SCARs: Non–dose-related, immunologic (T-cell-mediated) (Ref).
Onset: Delayed hypersensitivity reactions: Varied. Maculopapular rash usually occurs 6 days after the first or second administration (Ref). SJS/TEN and DRESS: 3 to 5 days (Ref). AGEP: 4 to 7 days after initiation was reported (Ref).
Risk factors (SJS/TEN):
• Radiotherapy (Ref)
• History of immune checkpoint inhibitor exposure (Ref)
Posterior reversible encephalopathy syndrome (PRES) has been associated with gemcitabine either as a single-agent or in combination with other chemotherapy (Ref). Patients may present with hypertension and/or various neurological issues, including headache, visual disturbances, altered mental status, lethargy, and/or seizure (Ref). Diagnosis is confirmed radiologically via magnetic resonance imaging wherein posterior cerebral white matter edema is typical (Ref).
Mechanism: Not clearly established; believed to be related to direct cellular damage to the vasculature of the blood brain barrier and endothelial damage, resulting in capillary leakage, failure of cerebral autoregulation, and vasogenic edema (Ref). These processes may be exacerbated by hypertension, particularly in the setting of rapidly increasing or fluctuating blood pressure, and/or fluid overload (Ref).
Onset: Delayed; case reports describe symptoms beginning ~8 to 18 weeks after initiation of treatment (Ref).
Risk factors:
• Concurrent platinum chemotherapy (Ref)
• Increased blood pressure (Ref)
• Females (Ref)
• Hypomagnesemia (Ref)
• Immunosuppression (calcineurin inhibitors) (Ref)
Treatment with gemcitabine has been associated with a range of pulmonary toxicities, including severe drug-induced lung injury (Ref). Mild to moderate dyspnea may occur during treatment, although development of severe pulmonary toxicity is rare. Fever, cough, and radiographic opacities are common concurrent symptoms. The pattern of pulmonary toxicity may be interstitial pneumonitis, pulmonary fibrosis, pulmonary edema, or acute respiratory distress syndrome (ARDS) (Ref). Despite drug discontinuation, lung injury may progress to fatal respiratory failure.
Mechanism: Non–dose-related (idiosyncratic); multiple etiologies of pulmonary toxicity secondary to gemcitabine have been proposed and mechanism may vary by patient. Most commonly, the mechanism of lung injury appears to be pulmonary edema secondary to endothelial dysfunction or damage within the alveolar capillaries causing vascular leakage (Ref). Others have suggested a cytokine-mediated inflammatory reaction as the underlying cause of increased permeability (Ref). Additionally, in patients exposed to concurrent or prior radiation therapy, gemcitabine may exacerbate or recall subclinical radiation-induced lung injury (Ref).
Onset: Varied; usually delayed, with initial presentation of symptoms weeks to months after initiation of gemcitabine (Ref). However, cases of rapid onset after a single dose of gemcitabine have also been reported (Ref).
Risk factors:
• Concurrent administration with other chemotherapy (bleomycin or taxane) (Ref)
• Pulmonary fibrosis (Ref)
• Presence of lung tumors (primary or metastatic) (Ref)
• Previous or concurrent radiation exposure (Ref)
• Asbestos exposure (Ref)
Treatment with gemcitabine in patients who have previously received radiation therapy has resulted in recurrence or recall of radiation toxicity, including mucositis, esophagitis, gastritis, dermatitis (including maculopapular eruptions, vesicle formation, and skin desquamation), myositis, and inflammation of internal organs or tissues, such as pneumonitis, colitis, or lymphangitis (Ref). In contrast with other chemotherapies associated with radiation recall phenomenon, gemcitabine has a greater propensity for affecting internal organs and tissues versus triggering cutaneous inflammation only. Some patients may experience little or no improvement of symptoms despite drug discontinuation and anti-inflammatory treatment (Ref).
Mechanism: Non–dose-related (idiosyncratic); radiation recall describes an inflammatory reaction that occurs in a previously irradiated location, after any acute injury has healed, in response to a second precipitating insult (Ref). Although the exact mechanism of radiation recall is uncertain, most have proposed an idiosyncratic phenomenon. Synergistic effects between radiation and gemcitabine are well-documented. Radiation treatment for cancer induces cellular death indiscriminately through ionization of atoms within the DNA leading to double-strand breaks and an inflammatory response within affected tissues (Ref). Treatment with gemcitabine has been associated with an inflammatory tumor response, and it induces cellular toxicity via inhibition of DNA synthesis, both of which may facilitate reactivation of latent radiation-induced tissue injury (Ref).
Onset: Varied; often reported after first gemcitabine treatment, although one series of six cases reported a range of 3 days to almost 8 months between the initiation of gemcitabine and radiation recall (median: 5.5 weeks) (Ref). By definition, radiation recall occurs >7 days after completion of radiation, with one series reporting an average of 58 days between completion of radiation and initiation of gemcitabine (Ref).
Risk factors:
• Shorter interval between completion of radiation and gemcitabine administration (Ref)
• Higher radiation dose (cumulative dose or dose per fraction) (Ref)
Cases of drug-induced thrombotic microangiopathy, both immune-mediated and not, have been reported in patients receiving gemcitabine (Ref). Cases are typically characterized by microangiopathic hemolytic anemia and thrombocytopenia. Occasionally, acute kidney injury may also be present (hemolytic-uremic syndrome). Less commonly, other organ system function, such as neurologic or cardiac, may be compromised (Ref).
Mechanism: Not clearly established; most cases seem to be dose-dependent, occurring either after repeated exposure or a large single dose. It is postulated that direct cellular damage to the vascular endothelium resulting in microthrombi and accumulation of kidney damage (Ref). Unlike other chemotherapeutic agents associated with thrombotic microangiopathy, complement activation as an additional cause of endothelial damage is commonly reported with gemcitabine (Ref). Rarely, an immune-mediated mechanism has been proposed for cases associated with gemcitabine, wherein drug-dependent antibodies enact damage to endothelial cells, neutrophils, and platelets (Ref).
Onset: Varied.
• Dose-dependent: Delayed; occurred after a median of 17.5 doses in one case series and after repeated exposure over a median of 8 months in another (Ref).
• Immune-mediated: Rapid; sudden onset of severe systemic symptoms, often within hours of drug exposure (Ref).
Risk factors:
• Median cumulative dose ~20 g/m2 (Ref)
• Prior or concurrent chemotherapy (Ref)
• New or worsening hypertension during gemcitabine treatment (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (≤13%), peripheral edema (20%)
Dermatologic: Alopecia (15%), skin rash (30%)
Gastrointestinal: Diarrhea (19%; grade 3: 1%), nausea and vomiting (69%; grades 3/4: 1% to 13%), stomatitis (11%; grade 3: <1%)
Genitourinary: Hematuria (35%), proteinuria (45%)
Hematologic & oncologic: Anemia (68%; grades 3/4: 1% to 7%), hemorrhage (17%; grades 3/4: <1%), neutropenia (63%; grades 3/4: 6% to 19%), thrombocytopenia (24%; grades 3/4: 1% to 4%)
Hepatic: Hyperbilirubinemia (13%), increased serum alanine aminotransferase (68%), increased serum alkaline phosphatase (55%), increased serum aspartate aminotransferase (67%)
Infection: Infection (16%)
Nervous system: Drowsiness (11%)
Renal: Increased blood urea nitrogen (16%)
Respiratory: Dyspnea (23%), flu-like symptoms (19%)
Miscellaneous: Fever (41%)
1% to 10%:
Local: Injection-site reaction (4%)
Nervous system: Paresthesia (10%)
Renal: Increased serum creatinine (8%)
Respiratory: Bronchospasm (<2%)
<1%: Infection: Sepsis
Frequency not defined:
Cardiovascular: Hypertension
Hematologic & oncologic: Hemolytic-uremic syndrome
Hypersensitivity: Nonimmune anaphylaxis
Renal: Kidney impairment
Postmarketing:
Cardiovascular: Acute myocardial infarction, arterial thrombosis (Ref), capillary leak syndrome (Ref), cardiac arrhythmia (including atrial fibrillation, supraventricular cardiac arrhythmia) (Ref), heart failure (Ref), vasculitis (peripheral)
Dermatologic: Acute generalized exanthematous pustulosis (Ref), bullous skin disease (Ref), cellulitis (including pseudocellulitis), desquamation, gangrene of skin and/or subcutaneous tissues, pruritus (Ref), Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Hyperammonemia (Ref)
Hematologic & oncologic: Petechia (Ref), thrombotic microangiopathy (Ref), thrombotic thrombocytopenic purpura (Ref)
Hepatic: Cholestatic hepatitis (Ref), hepatic failure (Ref), hepatic sinusoidal obstruction syndrome (Ref), hepatotoxicity (Ref)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Ref)
Nervous system: Cerebrovascular accident (Ref), posterior reversible encephalopathy syndrome (Ref)
Respiratory: Acute respiratory distress syndrome (Ref), eosinophilic pneumonitis, interstitial pneumonitis (Ref), pulmonary edema (Ref), pulmonary fibrosis
Miscellaneous: Radiation recall phenomenon (Ref)
Known hypersensitivity (including anaphylaxis) to gemcitabine or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: May cause bone marrow suppression (neutropenia, thrombocytopenia, and anemia), including grade 3 or 4 hematologic toxicity. Myelosuppression is generally the dose-limiting toxicity and is increased when used in combination with other chemotherapy.
• Capillary leak syndrome: Capillary leak syndrome with serious consequences has been reported, both with single-agent gemcitabine and with combination chemotherapy.
• Dermatologic toxicity: Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis), which can be life-threatening or fatal, have been associated with gemcitabine.
• Hemolytic uremic syndrome: Hemolytic uremic syndrome (HUS) has been reported; may lead to kidney failure and dialysis (including fatalities). Most fatal cases of kidney failure were due to HUS. Thrombotic microangiopathy other than HUS has also been reported. Assess for HUS in patients who develop anemia with microangiopathic hemolysis, elevation of bilirubin or lactate dehydrogenase, reticulocytosis, severe thrombocytopenia, and/or kidney failure (increased serum creatinine or BUN). Kidney failure may not be reversible despite gemcitabine discontinuation.
• Hepatotoxicity: Serious hepatotoxicity (including liver failure and death) has been reported with gemcitabine (when used alone or with other potentially hepatotoxic medications). The use of gemcitabine in patients with hepatic impairment (history of cirrhosis, hepatitis, or alcoholism) or in patients with hepatic metastases may lead to exacerbation of hepatic impairment.
• Hypersensitivity: Anaphylaxis and allergic reactions (including bronchospasm and anaphylactoid reactions) have been observed.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported, both with single-agent therapy and with combination chemotherapy. PRES may manifest with blindness, confusion, headache, hypertension, lethargy, seizure, and other visual and neurologic disturbances.
• Pulmonary toxicity: Pulmonary toxicity, including adult respiratory distress syndrome, interstitial pneumonitis, pulmonary edema, and pulmonary fibrosis, has been observed; may lead to respiratory failure (some fatal) despite gemcitabine discontinuation. The onset of pulmonary toxicity symptoms may be delayed up to 2 weeks beyond the last gemcitabine dose.
Special populations:
• Older adult: In some studies, higher rates of grades 3 and 4 neutropenia and thrombocytopenia have been observed in patients ≥65 years of age (compared to patients <65 years of age).
• Radiation therapy recipients: Gemcitabine is not recommended for use in combination with radiation therapy; radiation toxicity, including tissue injury, severe mucositis, esophagitis, or pneumonitis, has been reported with concurrent and nonconcurrent administration. Gemcitabine has radiosensitizing activity when gemcitabine and radiation therapy are given together or ≤7 days apart. Radiation recall may occur when gemcitabine and radiation therapy are given >7 days apart.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Infusion duration/frequency: Prolongation of the infusion duration to >60 minutes or more frequent than weekly dosing have been shown to alter the half-life and increase toxicity (hypotension, flu-like symptoms, myelosuppression, weakness). A fixed-dose rate (FDR) infusion rate of 10 mg/m2/minute has been studied in adults in order to optimize the pharmacokinetics (off-label); prolonged infusion times increase the intracellular accumulation of the active metabolite, gemcitabine triphosphate (Ko 2006; Tempero 2003). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ko 2006; Poplin 2009).
Infugem premix bags have been discontinued in the United States >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 200 mg/5.26 mL (5.26 mL); 200 mg/2 mL (2 mL); 1 g/10 mL (10 mL); 1 g/26.3 mL (26.3 mL); 1.5 g/15 mL (15 mL); 2 g/20 mL (20 mL); 2 g/52.6 mL (52.6 mL)
Solution, Intravenous [preservative free]:
Generic: 200 mg/5.26 mL (5.26 mL); 1 g/26.3 mL (26.3 mL); 2 g/52.6 mL (52.6 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Infugem: gemcitabine hydrochloride 1,200 mg/120 mL in NaCl 0.9% (120 mL [DSC]); gemcitabine hydrochloride 2,200 mg/220 mL in NaCl 0.9% (220 mL [DSC]); gemcitabine hydrochloride 2,000 mg/200 mL in NaCl 0.9% (200 mL [DSC]); gemcitabine hydrochloride 1,300 mg/130 mL in NaCl 0.9% (130 mL [DSC]); gemcitabine hydrochloride 1,400 mg/140 mL in NaCl 0.9% (140 mL [DSC]); gemcitabine hydrochloride 1,500 mg/150 mL in NaCl 0.9% (150 mL [DSC]); gemcitabine hydrochloride 1,600 mg/160 mL in NaCl 0.9% (160 mL [DSC]); gemcitabine hydrochloride 1,700 mg/170 mL in NaCl 0.9% (170 mL [DSC]); gemcitabine hydrochloride 1,800 mg/180 mL in NaCl 0.9% (180 mL [DSC]) [latex free]
Infugem: gemcitabine hydrochloride 1,900 mg/190 mL in NaCl 0.9% (190 mL [DSC])
Solution Reconstituted, Intravenous:
Generic: 200 mg (1 ea); 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 200 mg (1 ea); 1 g (1 ea)
Yes
Solution (Gemcitabine HCl Intravenous)
1 g/10 mL (per mL): $7.92
1 g/26.3 mL (per mL): $1.00 - $2.07
1.5 g/15 mL (per mL): $6.60
2 g/20 mL (per mL): $7.04
2 g/52.6 mL (per mL): $1.02 - $2.07
200 mg/2 mL (per mL): $26.40
200 mg/5.26 mL (per mL): $1.14 - $2.13
Solution (reconstituted) (Gemcitabine HCl Intravenous)
1 g (per each): $50.26 - $800.23
2 g (per each): $136.18 - $154.44
200 mg (per each): $9.29 - $14.46
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 38 mg/mL (5.3 mL, 26.3 mL, 52.6 mL); 40 mg/mL (5 mL, 25 mL, 50 mL)
Solution Reconstituted, Intravenous:
Generic: 1 g (1 ea); 2 g (1 ea)
IV: For labeled indications, infuse over 30 minutes; if utilizing premixed infusion bags and 2 premixed bags are required, infuse the total volume of both bags over 30 minutes (follow manufacturer’s instructions to spike premixed bag and add administration set).
For off-label uses, infusion times may vary (refer to specific references). Note: Prolongation of the infusion time >60 minutes has been shown to increase toxicity. Gemcitabine has been administered at a fixed-dose rate (FDR) infusion rate of 10 mg/m2/minute to optimize the pharmacokinetics (off-label); prolonged infusion times increase the intracellular accumulation of the active metabolite, gemcitabine triphosphate (Ref). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ref).
Bladder cancer (transitional cell; off-label use): For intravesicular (bladder) instillation (off-label route), gemcitabine was diluted in 50 to 100 mL normal saline; patients were instructed to retain in the bladder for 1 hour (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Lyophilized powder: Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Reconstituted vials are stable for 24 hours at room temperature (discard if not used within 24 hours of reconstitution). Do not refrigerate (may form crystals).
Concentrated solution for injection (vials): Varies by manufacturer; refer to product labeling.
Premixed infusion solutions: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze (may result in crystallization).
Solutions prepared/diluted for infusion in NS are stable for 24 hours at room temperature. Do not refrigerate (may result in crystallization).
Gemcitabine may be confused with gemtuzumab ozogamicin
Gemzar may be confused with Zinecard
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Multiple concentrations: Gemcitabine is available in multiple formulations and concentrations; verify product and concentration prior to admixture to assure appropriate dose preparation.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bleomycin: Gemcitabine may increase adverse/toxic effects of Bleomycin. The risk of pulmonary toxicity may be increased. Risk C: Monitor
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Cedazuridine: May increase serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fluorouracil (Systemic): Gemcitabine may increase serum concentration of Fluorouracil (Systemic). Risk C: Monitor
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
PACLitaxel (Protein Bound): May increase adverse/toxic effects of Gemcitabine. Specifically, the risk for thrombotic microangiopathy may be increased with this combination. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Warfarin: Gemcitabine may increase anticoagulant effects of Warfarin. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 6 months after the final gemcitabine dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the final gemcitabine dose.
Based on the mechanism of action and on findings from animal reproduction studies, in utero exposure to gemcitabine may cause fetal harm.
Information related to the use of gemcitabine in pregnancy is limited (Lubner 2011; Wiesweg 2014).
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).
Gemcitabine is a pyrimidine antimetabolite that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase, cell cycle-specific for the S-phase of the cycle (also blocks cellular progression at G1/S-phase). Gemcitabine is phosphorylated intracellularly by deoxycytidine kinase to gemcitabine monophosphate, which is further phosphorylated to active metabolites gemcitabine diphosphate and gemcitabine triphosphate. Gemcitabine diphosphate inhibits DNA synthesis by inhibiting ribonucleotide reductase; gemcitabine triphosphate incorporates into DNA and inhibits DNA polymerase.
Distribution: Widely distributed into tissues; present in ascitic fluid; Vd: Infusions <70 minutes: 50 L/m2; Long infusion times (70 to 285 minutes): 370 L/m2
Protein binding: Negligible
Metabolism: Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites; the metabolites are then converted to inactive uracil metabolite (dFdU).
Half-life elimination:
Gemcitabine: Infusion time ≤70 minutes: 42 to 94 minutes; infusion time 3 to 4 hours: 4 to 10.5 hours (affected by age and gender)
Metabolite (gemcitabine triphosphate), terminal phase: 1.7 to 19.4 hours
Time to peak, plasma: 30 minutes after completion of infusion
Excretion: Urine (92% to 98%; primarily as inactive uracil metabolite [dFdU]); feces (<1%)
Older adult: The lower clearance in geriatric patients results in higher concentrations of gemcitabine for any given dose.
Sex: Gemcitabine clearance is lower and the half-life is longer in females (compared with males).
