Gemcitabine is a chemotherapy medication that is used to treat various types of cancer. It is marketed under the brand name Gemzar. Gemcitabine is classified as an antimetabolite, which means it interferes with the growth and spread of cancer cells by disrupting their DNA synthesis.

Gemcitabine (Gemzar) is a nucleoside analog that inhibits ribonucleotide reductase. It is classified as an antimetabolite. It is used in various chemotherapeutic regimens used to treat breast cancer, testicular, ovarian, bladder, pancreatic, and lung cancer.

Gemcitabine Uses: 

• Metastatic Breast cancer:
  • It is indicated in the treatment of metastatic breast cancer as a first-line agent, combined with paclitaxel that is resistant to anthracycline-containing agents.
• Locally advanced/ Inoperable, metastatic non-small cell lung cancer:
  • It is indicated in the treatment of inoperable locally advanced or metastatic (Stage IIIA, stage IIIB and stage IV) non-small cell lung carcinoma as a first-line agent, combined with cisplatin.
• Advanced Ovarian cancer:
  • Gemcitabine (combined with carboplatin) is used in the treatment of advanced ovarian cancer that has relapsed at least 6 months following completion of platinum-based chemotherapy
• Metastatic or Locally advanced Pancreatic cancer:
  • Gemcitabine is indicated in pancreatic adenocarcinoma which is locally advanced (stage II or III, non-resectable) or metastatic (stage IV) as a first-line agent in patients previously treated with fluorouracil.
• Off Label Use of Gemcitabine in Adults:
  • Advanced or metastatic Bladder cancer
  • Refractory transitional cell Bladder cancer
  • Recurrent or persistent Cervical cancer
  • Refractory Ewing sarcoma
  • Head and neck cancer: metastatic or advanced nasopharyngeal carcinoma
  • Advanced Hepatobiliary cancer
  • Relapsed Hodgkin lymphoma
  • Malignant pleural mesothelioma
  • Relapsed or refractory Non-Hodgkin lymphoma
  • Refractory Osteosarcoma
  • Pancreatic cancer as adjuvant therapy
  • Metastatic Renal cell carcinoma
  • Refractory or relapsed Small cell lung cancer
  • Advanced Soft tissue sarcoma.
  • Refractory Germ cell Testicular cancer
  • Refractory Thymic malignancies
  • Unknown-primary carcinoma
  • Uterine cancer

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Gemcitabine (Gemzar) Dose in Adult

Note: When using gemcitabine, it's important to follow certain guidelines to avoid increased toxicity. Infusions should not exceed 60 minutes, and the medication should not be administered more than once a week. If premixed infusion bags are being used, make sure to choose ones that allow for a variance of ≤5% of the calculated dose based on body surface area (BSA). Additionally, avoid using premixed infusion bags for patients who require a dose size of less than 1,200 mg/dose and opt for a different formulation instead. Following these recommendations helps ensure safe and effective use of gemcitabine.

Gemcitabine (Gemzar) Dose in the treatment of metastatic Breast cancer:

Combination Therapy (with paclitaxel):

• Intravenous (IV) administration
• Dose: 1,250 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Continue the cycle until disease progression or if unacceptable side effects occur (based on Albain, 2008 study)

Single-Agent Therapy (Off-label dosing):

• IV administration
• Dose: 800 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• This dosing regimen is not officially approved but has been used in clinical practice (based on Carmichael, 1995 study)

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Gemcitabine (Gemzar) Dose in the treatment of locally advanced, metastatic, or inoperable Non-small cell lung cancer:

Combination Therapy with Cisplatin:

• Intravenous (IV) administration
• Dose Option 1: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Repeat the cycle every 28 days
• Dose Option 2: 1,250 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days

Off-label Dosing/Combinations:

• In combination with carboplatin:
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
  • Repeat the cycle for up to 4 cycles
  • Dosing regimen may vary based on the specific study.
• In combination with docetaxel:
  • Dose: 1,000 mg/m
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
  • Repeat the cycle for 8 cycles.
• In combination with vinorelbine:
  • Dose: 1,000 mg/m
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
  • Repeat the cycle for 6 cycles.

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Gemcitabine (Gemzar) Dose in the treatment of advanced or metastatic Ovarian cancer:

Combination Therapy with Carboplatin:

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days

Off-label Single-Agent Therapy:

• IV administration
• Dose: 1,000 mg/m
• Infusion time: 30 to 60 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days
• This dosing regimen is not officially approved but has been used in clinical practice.

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Gemcitabine (Gemzar) Dose in the treatment of locally advanced or metastatic pancreatic cancer:

Initial Therapy:

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Once weekly for 7 weeks followed by a 1-week rest period
• After the rest period, continue with once-weekly treatment for 3 weeks out of every 4 weeks

Off-label Dosing/Combinations:

• In combination with erlotinib:
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Weekly for up to 7 weeks followed by a 1-week rest period
  • After the rest period, continue with once-weekly treatment for 3 weeks out of every 4 weeks.
• In combination with capecitabine:
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle.
• In combination with cisplatin:
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1 and 15 of a 28-day treatment cycle.
• In combination with oxaliplatin:
  • Dose: 1,000 mg/m
  • Infusion time: Infused at 10 mg/m/minute
  • Treatment schedule: Given every 14 days.
• In combination with paclitaxel (protein-bound):
  • Dose: 1,000 mg/m
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle.

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Gemcitabine (Gemzar) Dose in the treatment of Pancreatic cancer (adjuvant therapy) (off-label):

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Duration: 6 cycles
• Initiation of treatment: Begin within 12 weeks of surgical resection, as recommended by the study conducted by Neoptolemos in 2017.
• American Society of Clinical Oncology (ASCO) guidelines suggest initiating treatment within 8 weeks of resection.

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Gemcitabine (Gemzar Dose in the treatment of Bladder cancer (off-label):

Advanced or Metastatic Bladder Cancer, in combination with cisplatin:

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Infusion time: 30 to 60 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Repeat the cycle every 28 days.

Advanced or Metastatic Bladder Cancer, in combination with carboplatin:

• IV administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle until disease progression or if unacceptable toxicity occurs.

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Gemcitabine (Gemzar) Dose in the treatment of Refractory Transitional cell carcinoma:

Intravesicular Instillation (directly into the bladder):

• Dose: 2,000 mg
• Dilution: Mixed with 100 mL of normal saline (NS)
• Retention Time: Retain the solution in the bladder for 1 hour
• Treatment Schedule: Administered twice weekly for 3 weeks
• Repeat the cycle every 4 weeks
• Duration: At least 2 cycles of treatment

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Gemcitabine (Gemzar) Dose in the treatment of recurrent or persistent Cervical cancer (off-label):

In combination with cisplatin:

• Intravenous (IV) administration
• Dose Option 1: 1,000 mg/m
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days (according to Monk, 2009 study)
• Dose Option 2: 1,250 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days (according to Burnett, 2000 study)

Single-Agent Therapy:

• IV administration
• Dose: 800 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Repeat the cycle every 28 days (according to Schilder, 2005 study)
• In combination with cisplatin:
  • IV administration
  • Dose: 800 mg/m
  • Treatment schedule: Given on days 1 and 8 of a 28-day treatment cycle
  • Repeat the cycle every 28 days (according to Brewer, 2006 study)

It's important to note that these dosing regimens are considered off-label, meaning they are not officially approved for cervical cancer treatment by regulatory authorities.

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Gemcitabine (Gemzar) Dose in the treatment of advanced or metastatic head and neck cancer: nasopharyngeal, (off-label):

IV administration:

• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Option 1:
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
  • Repeat the cycle every 28 days (according to Zhang, 2008 study)
• Option 2:
  • In combination with vinorelbine:
    • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle (according to Chen, 2012 study)

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of advanced or metastatic nasopharyngeal head and neck cancer.

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Gemcitabine (Gemzar) Dose in the treatment of advanced Hepatobiliary cancer, (off-label):

In combination with cisplatin:

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days.

In combination with capecitabine:

• IV administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days.

In combination with oxaliplatin:

• IV administration
• Dose: 1,000 mg/m
• Infusion time: Administered at 10 mg/m/minute
• Treatment schedule: Given every 2 weeks
• Repeat the cycle as per the specific regimen.

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of advanced hepatobiliary cancer.

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Gemcitabine (Gemzar) Dose in the treatment of relapsed Hodgkin lymphoma (off-label):

In combination with vinorelbine and doxorubicin liposomal:

• Intravenous (IV) administration
• Dose: 1,000 mg/m (800 mg/m for post-transplant patients)
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days (according to Bartlett, 2007 study)

In combination with ifosfamide, mesna, vinorelbine, and prednisolone:

• IV administration
• Dose: 800 mg/m
• Treatment schedule: Given on days 1 and 4 of a 21-day treatment cycle
• Repeat the cycle every 21 days (according to Santoro, 2007 study)

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of relapsed Hodgkin lymphoma.

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Gemcitabine (Gemzar) Dose in the treatment of Malignant pleural mesothelioma (off-label use; in combination with cisplatin):

IV administration:

• Dose Option 1: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Repeat the cycle for up to 6 cycles.

IV administration:

• Dose Option 2: 1,250 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle for up to 6 cycles.

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of malignant pleural mesothelioma.

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Gemcitabine (Gemzar) Dose in the treatment of refractory non-Hodgkin lymphoma (off-label):

In combination with cisplatin and dexamethasone:

• Intravenous (IV) administration
• Dose: 1,000 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Repeat the cycle every 21 days.

In combination with oxaliplatin and rituximab:

• IV administration
• Dose: 1,000 mg/m (specific dosing interval not provided)
• Treatment schedule: Given every 15 to 21 days.

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of refractory non-Hodgkin lymphoma.

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Gemcitabine (Gemzar) Dose in the treatment of Sarcomas (off-label):

Ewing sarcoma, refractory (in combination with docetaxel):

• Intravenous (IV) administration
• Dose: 675 mg/m
• Infusion time: 90 minutes
• Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.

Osteosarcoma, refractory:

• Option 1 (in combination with docetaxel):
  • IV administration
  • Dose: 675 mg/m
  • Infusion time: 90 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.
• Option 2:
  • IV administration
  • Dose: 1,000 mg/m
  • Treatment schedule: Weekly for 7 weeks followed by 1 week of rest; then weekly for 3 weeks out of every 4 weeks.

Soft tissue sarcoma, advanced:

• Option 1 (in combination with vinorelbine):
  • IV administration
  • Dose: 800 mg/m
  • Infusion time: 90 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.
• Option 2 (in combination with docetaxel):
  • IV administration
  • Dose: 675 mg/m
  • Infusion time: 90 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.
• Option 3 (in combination with docetaxel):
  • IV administration
  • Dose: 900 mg/m
  • Infusion time: 90 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of sarcomas.

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Gemcitabine (Gemzar) Dose in the treatment of refractory or relapsed small cell lung cancer (off-label): 

• Intravenous (IV) administration
• Dose: 1,000 to 1,250 mg/m
• Infusion time: 30 minutes
• Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle
• Used as a single agent.

Please note that this dosing regimen is considered off-label, as it is not officially approved for the treatment of refractory or relapsed small cell lung cancer.

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Gemcitabine (Gemzar) Dose in the treatment of Testicular cancer, refractory germ cell (off-label):

Intravenous (IV) administration

• Dose option 1 (in combination with oxaliplatin):
  • Dose: 1,000 to 1,250 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle.
• Dose option 2 (in combination with paclitaxel):
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle for up to 6 cycles
• Dose option 3 (in combination with oxaliplatin and paclitaxel):
  • Dose: 800 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of refractory germ cell testicular cancer.

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Gemcitabine (Gemzar) Dose in the treatment of Unknown-primary, adenocarcinoma (off-label): IV

Intravenous (IV) administration

• Dose option 1 (in combination with cisplatin):
  • Dose: 1,250 mg/m
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Dose option 2 (in combination with docetaxel):
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle for up to 6 cycles

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of unknown-primary adenocarcinoma.

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Gemcitabine (Gemzar) Dose in the treatment of Uterine cancer (off-label):

Intravenous (IV) administration

• Dose option 1 (in combination with docetaxel):
  • Dose: 900 mg/m
  • Infusion time: 90 minutes
  • Treatment schedule: Given on days 1 and 8 of a 21-day treatment cycle
• Dose option 2:
  • Dose: 1,000 mg/m
  • Infusion time: 30 minutes
  • Treatment schedule: Given on days 1, 8, and 15 of a 28-day treatment cycle

Please note that these dosing regimens are considered off-label, as they are not officially approved for the treatment of uterine cancer.

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Dosing adjustment for toxicity: Dosing adjustment on basis of adult patients

Toxicity Type	Breast Cancer	Non-Small Cell Lung Cancer	Ovarian Cancer	Hematologic Toxicity in Previous Cycle
Nonhematologic Toxicity
(Severe grade 3 or 4)	Hold or decrease by 50%	Hold or decrease by 50%	Hold or decrease by 50%
Severe Pulmonary Toxicity	Permanently discontinue	Permanently discontinue	Permanently discontinue
Severe Hepatotoxicity	Permanently discontinue	Permanently discontinue	Permanently discontinue
Hemolytic Uremic Syndrome (HUS)	Permanently discontinue	Permanently discontinue	Permanently discontinue
Capillary Leak Syndrome (CLS)	Permanently discontinue	Permanently discontinue	Permanently discontinue
Posterior Reversible Encephalopathy Syndrome	Permanently discontinue	Permanently discontinue	Permanently discontinue
Hematologic Toxicity
Breast Cancer - Day 1	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³
	Hold if AGC <1,500/mm³ or platelet count <100,000/mm³	Hold if AGC <500/mm³ or platelet count <50,000/mm³	Delay treatment cycle if AGC <1,500/mm³ or platelet count <100,000/mm³
Breast Cancer - Day 8	Administer 100% if AGC ≥1,200/mm³ and platelet count >75,000/mm³	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³
	Administer 75% if AGC 1,000 to 1,199/mm³ or platelet count 50,000 to 75,000/mm³	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³	Administer 50% if AGC 1,000 to 1,499/mm³ or platelet count 75,000 to 99,999/mm³
	Administer 50% if AGC 700 to 999/mm³ and platelet count ≥50,000/mm³	Administer 50% if AGC <500/mm³ or platelet count <50,000/mm³	Hold if AGC <1,000/mm³ or platelet count <75,000/mm³
	Hold if AGC <700/mm³ or platelet count <50,000/mm³	Hold if AGC <500/mm³ or platelet count <50,000/mm³
Non-Small Cell Lung Cancer
Day 1	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³
	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³	Delay treatment cycle if AGC <1,500/mm³ or platelet count <100,000/mm³
Ovarian Cancer
Day 1	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³		Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³
	Delay treatment cycle if AGC <1,500/mm³ or platelet count <100,000/mm³		Delay treatment cycle if AGC <1,500/mm³ or platelet count <100,000/mm³
Day 8	Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³		Administer 100% if AGC ≥1,500/mm³ and platelet count ≥100,000/mm³
	Administer 50% if AGC 1,000 to 1,499/mm³ or platelet count 75,000 to 99,999/mm³		Administer 50% if AGC <1,000/mm³ or platelet count <75,000/mm³
	Hold if AGC <1,000/mm³ or platelet count <75,000/mm³		Hold if AGC <1,000/mm³ or platelet count <75,000/mm³
Hematologic Toxicity in Previous Cycle
Initial Occurrence	Permanently reduce to 800 mg/m² on days 1 and 8 if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, febrile neutropenia, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity	Permanently reduce to 800 mg/m² on days 1 and 8 if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, neutropenic fever, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity	Permanently reduce to 800 mg/m² on days 1 and 8 if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, febrile neutropenia, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity
Subsequent Occurrence	Permanently reduce to 800 mg/m² and administer on day 1 only if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, neutropenic fever, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity	Permanently reduce to 800 mg/m² and administer on day 1 only if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, neutropenic fever, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity	Permanently reduce to 800 mg/m² and administer on day 1 only if AGC <500/mm³ for >5 days, AGC <100/mm³ for >3 days, neutropenic fever, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity
Pancreatic Cancer
	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³	Administer 100% if AGC ≥1,000/mm³ and platelet count ≥100,000/mm³
	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³	Administer 75% if AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³
	Hold if AGC <500/mm³ or platelet count <50,000/mm³	Hold if AGC <500/mm³ or platelet count <50,000/mm³	Hold if AGC <500/mm³ or platelet count <50,000/mm³

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Gemcitabine (Gemzar) Dose in Children

Note:

• It is important to consult the specific dosing details for gemcitabine when used in combination with other medications.
• It is advised to avoid prolonging the infusion time beyond 60 minutes and to not administer it more frequently than once a week, as these can increase the risk of side effects.
• Gemcitabine is known to have a low risk of causing nausea and vomiting, but to prevent these symptoms, it is recommended to use antiemetic medications

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Gemcitabine (Gemzar) Dose in the treatment of refractory or relapsed Hodgkin lymphoma:  

Children ≥10 years and Adolescents:

• IV: 1,000 mg/m /dose over 100 minutes on days 1 and 8
• In combination with vinorelbine
• Repeat cycle every 21 days

Adolescents ≥17 years:

• IV: 1,000 mg/m /dose over 60 minutes on days 1, 8, and 15
• In combination with vinorelbine
• Repeat cycle every 28 days

Adolescents ≥17 years:

• IV: 800 mg/m /dose on days 1 and 4
• In combination with ifosfamide and vinorelbine
• Repeat cycle every 21 days

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Gemcitabine (Gemzar) Dose in the treatment of refractory or relapsed Sarcomas (including Ewing sarcoma, osteosarcoma): Limited data available:

Children ≥3 years and Adolescents:

• IV: 675 or 1,000 mg/m /dose over 90 minutes on days 1 and 8
• In combination with docetaxel
• Repeat cycle every 21 days

Children ≥3 years and Adolescents:

• IV: 1,000 mg/m /dose over 30 minutes on days 1 and 8
• In combination with oxaliplatin and irinotecan
• Repeat cycle every 28 days

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Gemcitabine (Gemzar) Dose in the treatment of refractory or relapsed solid tumors: Limited data available:

Children ≥1 year and Adolescents:

• IV: 1,000 mg/m /dose over 30 minutes on days 1 and 8
• In combination with oxaliplatin and irinotecan
• Repeat cycle every 28 days

Children ≥1 year and Adolescents:

• IV: 1,000 mg/m /dose over 100 minutes on day 1
• In combination with oxaliplatin
• Repeat cycle every 14 days

Note: Dosage reductions for toxicity (Geoerger 2011):

• If experiencing grade 3/4 nonhematological toxicity, grade 4 neutropenia with documented infection or lasting more than 7 days, grade 3/4 thrombocytopenia lasting more than 7 days or requiring platelets for more than 7 days, or a delay of the next cycle of 14 days or more, the following dosage reduction should be considered:
  • Initial reduction: 800 mg/m /dose over 80 minutes
  • If necessary, a second reduction: 600 mg/m /dose

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Gemcitabine (Gemzar) Dose in the treatment of refractory Germ cell tumor: Limited data available:

Adolescents ≥16 years:

• Limited data is available for the use of gemcitabine in the treatment of refractory germ cell tumors.
• In adolescents aged 16 years and above, the recommended dose is 1,200 mg/m² given intravenously over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle.
• This cycle can be repeated for up to 6 cycles.

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Gemcitabine Pregnancy Category: D

• Gemcitabine can be harmful to a developing fetus if taken during pregnancy, so it's important for females of reproductive age to confirm they are not pregnant before starting treatment.
• They should use reliable contraception during treatment and for six months after the last dose.
• Males who have female partners capable of becoming pregnant should also use contraception during treatment and for three months after the last dose.
• Studies in animals suggest that gemcitabine may affect male fertility.

Use of gemcitabine during lactation

• The presence of gemcitabine in breast milk is not known.
• To ensure the safety of the breastfeeding infant, it is recommended to avoid breastfeeding during gemcitabine treatment and for at least one week after the final dose.
• This precaution is necessary to minimize the potential for serious side effects in the nursing baby.
• It is advisable to explore alternative feeding options during this period.

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Gemcitabine (Gemzar) Dose in Kidney disease:

Dosage adjustments for gemcitabine are not specified in the manufacturer's labeling. However, if severe renal toxicity or hemolytic uremic syndrome (HUS) occurs during gemcitabine treatment, it should be discontinued.

• Mild-to-severe renal impairment:
  • For patient with mild-to-severe renal impairment, no dosage adjustment is necessary according to studies conducted by Janus in 2010 and Li in 2007.
• ESRD (on hemodialysis):
  • For patients with end-stage renal disease (ESRD) receiving hemodialysis, it is recommended to start hemodialysis 6 to 12 hours after gemcitabine infusion.

Gemcitabine (Gemzar) Dose in Liver disease:

The manufacturer's labeling does not provide specific dosage adjustments for gemcitabine. However, if severe hepatotoxicity occurs during treatment, it is recommended to discontinue gemcitabine.

• Transaminases elevated (with normal bilirubin):
  • In cases where transaminases are elevated but bilirubin levels are normal, no dosage adjustment is necessary.
• Serum bilirubin >1.6 mg/dL:
  • If serum bilirubin levels exceed 1.6 mg/dL, an initial dose of 800 mg/m² may be used, and dose escalation may be considered if it is well tolerated.

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Frequency of adverse reactions reported for single-agent use of gemcitabine only.

Common Side Effects of Gemcitabine (Gemzar):

• Cardiovascular:
  • Peripheral Edema
  • Edema
• Central Nervous System:
  • Drowsiness
• Dermatologic:
  • Skin Rash
  • Alopecia
• Gastrointestinal:
  • Nausea And Vomiting
  • Diarrhea
  • Stomatitis
• Genitourinary:
  • Proteinuria
  • Hematuria
• Hematologic & Oncologic:
  • Anemia
  • Neutropenia
  • Thrombocytopenia
  • Hemorrhage
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Hyperbilirubinemia
• Infection:
  • Infection
• Renal:
  • Increased Blood Urea Nitrogen
• Respiratory:
  • Dyspnea
  • Flu-Like Symptoms
• Miscellaneous:
  • Fever

Less Common Side Effects Of Gemcitabine (Gemzar):

• Central Nervous System:
  • Paresthesia
• Local:
  • Injection Site Reaction
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Bronchospasm

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Contraindications to Gemcitabine (Gemzar):

If an individual has a known hypersensitivity or allergic reaction to gemcitabine or any of its components, it is important to avoid using gemcitabine. Hypersensitivity reactions can range from mild symptoms such as rash and itching to severe reactions including difficulty breathing and anaphylaxis.

Warnings and precautions

Suppression of bone marrow

• Gemcitabine can lead to bone marrow suppression, which refers to a decrease in the production of blood cells in the bone marrow.
• This can result in low levels of white blood cells (neutropenia), platelets (thrombocytopenia), and red blood cells (anemia).
• The severity of this hematologic toxicity can range from mild to severe (grade 3 or 4).
• In combination with other chemotherapy drugs, the risk of myelosuppression is further increased.
• It is important to regularly monitor blood counts to assess the impact on blood cell levels.
• If significant hematologic toxicity occurs, treatment interruption, dosage reduction, or even discontinuation of gemcitabine may be necessary.
• The management of hematologic toxicity should be determined by based on the individual patient's condition and response to treatment.

Capillary leak syndrome

• Capillary leak syndrome (CLS) is a rare but serious condition that has been reported with gemcitabine treatment, both when used alone and in combination with other chemotherapy drugs.
• CLS is characterized by the leakage of fluid and proteins from blood vessels into surrounding tissues, leading to fluid accumulation and potentially severe consequences.
• If a patient develops capillary leak syndrome while receiving gemcitabine, it is recommended to permanently discontinue gemcitabine treatment.
• Prompt recognition and appropriate management of CLS are essential to prevent further complications and ensure patient safety.
• Patients should be closely monitor when receiving gemcitabine for any signs or symptoms of capillary leak syndrome and take appropriate action if it occurs.

Hemolytic uremic Syndrome:

• Hemolytic uremic syndrome (HUS) is a rare but serious condition that has been reported in association with gemcitabine treatment.
• HUS can lead to renal failure and the need for dialysis, and in severe cases, it can be life-threatening.
• To monitor for HUS, healthcare professionals should observe for signs of anemia with microangiopathic hemolysis, which may include elevated bilirubin or LDH levels, reticulocytosis, severe thrombocytopenia, and/or renal failure indicated by increased serum creatinine or blood urea nitrogen (BUN) levels.
• Renal function should be assessed before starting gemcitabine treatment and periodically during the course of treatment.
• If HUS or severe renal impairment occurs, gemcitabine should be permanently discontinued.
• It is important to note that even after stopping gemcitabine, renal failure may not be reversible.
• Close monitoring and prompt medical intervention are crucial in managing HUS and its potential complications.

Hepatotoxicity

• Gemcitabine treatment has been associated with serious hepatotoxicity, including liver failure and fatalities.
• This risk applies to gemcitabine when used alone or in combination with other medications that can cause liver damage.
• Patients with pre-existing hepatic impairment, such as a history of cirrhosis, hepatitis, or alcoholism, or those with hepatic metastases may be at higher risk for worsening liver function with gemcitabine.
• It is important to monitor liver function tests before starting gemcitabine and periodically throughout the treatment course.
• If elevated levels of bilirubin are observed, dose adjustments may be considered.
• If severe liver injury occurs, gemcitabine should be permanently discontinued.
• Close monitoring of hepatic function and prompt action in response to any signs of liver injury are crucial for patient safety.

Hypersensitivity

• Gemcitabine can potentially cause hypersensitivity reactions, including anaphylaxis and allergic reactions.
• These reactions may manifest as bronchospasm (constriction of the airways) or anaphylactoid reactions (resembling anaphylaxis but without involving an immune response).
• It is important to be aware of the signs and symptoms of hypersensitivity, such as difficulty breathing, chest tightness, swelling of the face or throat, rash, itching, or hives.
• If a hypersensitivity reaction occurs, immediate medical attention should be sought.
• Patients should be carefully monitor when receiving gemcitabine treatment and take appropriate measures to manage and treat any allergic or anaphylactic reactions.

The posterior reversible syndrome of encephalopathy:

• Posterior reversible encephalopathy syndrome (PRES) has been observed in patients receiving gemcitabine, both as a single-agent therapy and in combination with other chemotherapy drugs.
• PRES is characterized by symptoms such as blindness, confusion, headache, hypertension (high blood pressure), lethargy, seizures, and various visual and neurological disturbances.
• If a diagnosis of PRES is confirmed through magnetic resonance imaging (MRI) scans, it is recommended to permanently discontinue gemcitabine therapy.
• Prompt recognition and appropriate management of PRES are crucial to ensure patient safety and prevent further complications.

Toxicity in the lungs:

• Gemcitabine treatment has been associated with pulmonary toxicity, which can manifest as various conditions including adult respiratory distress syndrome, interstitial pneumonitis, pulmonary edema, and pulmonary fibrosis.
• These pulmonary complications may result in respiratory failure, and in some cases, they can be fatal even after discontinuing gemcitabine.
• It is important to note that symptoms of pulmonary toxicity may appear up to two weeks after the last dose of gemcitabine.
• If patients experience unexplained difficulty in breathing (dyspnea), with or without bronchospasm, or show signs of severe pulmonary toxicity, it is recommended to permanently discontinue gemcitabine treatment.
• Prompt recognition and appropriate management are crucial in addressing these pulmonary complications and ensuring patient well-being.

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Gemcitabine: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Fluorouracil (Systemic)	Gemcitabine may increase the serum concentration of Fluorouracil (Systemic).
Fluorouracil (Topical)	Gemcitabine may increase the serum concentration of Fluorouracil (Topical).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Warfarin	Gemcitabine may enhance the anticoagulant effect of Warfarin.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Bleomycin	Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
FingolimodI	mmunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lenograstim	Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic Agents may diminish the therapeutic effect 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.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Palifermin	May enhance the adverse/toxic effect 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.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Cladribine	Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

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Monitoring parameters:

Complete Blood Count (CBC) with differential and platelet count:

• It is important to regularly monitor blood cell counts before each gemcitabine dose.
• This helps assess the impact on bone marrow and detect any signs of hematologic toxicity such as neutropenia, thrombocytopenia, or anemia.

Hepatic and renal function:

• Prior to starting gemcitabine therapy, it is necessary to evaluate the liver and kidney function.
• Periodic monitoring of these parameters during treatment ensures the drugs are being properly metabolized and eliminated from the body.

Electrolytes:

• When gemcitabine is used in combination with platinum-based chemotherapy like cisplatin, monitoring electrolyte levels, including potassium, magnesium, and calcium, is crucial.
• This helps maintain the balance of these essential minerals in the body.

Pregnancy test:

• Before initiating gemcitabine treatment in females of reproductive potential, a pregnancy test should be conducted to confirm the absence of pregnancy.
• Gemcitabine may pose risks to the developing fetus, so effective contraception should be used during treatment and for a specified duration afterward.

Pulmonary function:

• Regular monitoring of pulmonary function is recommended during gemcitabine treatment.
• This helps detect any signs of pulmonary toxicity, such as respiratory distress, interstitial pneumonitis, or pulmonary fibrosis, and allows for timely intervention if necessary.

Capillary leak syndrome and posterior reversible encephalopathy syndrome:

• Close attention should be paid to any signs or symptoms of capillary leak syndrome, such as fluid retention or edema, as well as posterior reversible encephalopathy syndrome, which can cause visual and neurologic disturbances.
• Early recognition of these conditions is important, and gemcitabine treatment should be discontinued if they are confirmed.

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How to administer Gemcitabine (Gemzar)?

Intravenous (IV) Administration:

• For labeled indications, gemcitabine should be infused over a period of 30 minutes. If two premixed infusion bags are needed, the total volume of both bags should still be infused over 30 minutes.
• It's important to note that for off-label uses, the infusion times may vary, and specific references should be consulted.
• It has been shown that prolonging the infusion time beyond 60 minutes can increase the risk of toxicity.
• In some cases, gemcitabine has been administered at a fixed-dose rate (FDR) infusion rate of 10 mg/m²/minute to optimize its pharmacokinetics (off-label use). However, it's worth mentioning that this prolonged infusion has been associated with higher rates of grade 3/4 hematologic toxicity.

Bladder Cancer (Transitional Cell; Off-label Use):

• For intravesicular (bladder) instillation (off-label route), gemcitabine is diluted in 50 to 100 mL of normal saline.
• Patients are instructed to retain the gemcitabine solution in the bladder for one hour.

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Mechanism of action of Gemcitabine (Gemzar):

• Gemcitabine is a type of medication known as a pyrimidine antimetabolite.
• It works by interfering with the synthesis of DNA, which is essential for cell growth and division.
• Specifically, gemcitabine inhibits two important enzymes involved in DNA synthesis: DNA polymerase and ribonucleotide reductase.
• It has a cell cycle-specific action, primarily affecting the S-phase of the cell cycle and also blocking cellular progression at the G1/S-phase boundary.
• After being taken up by cells, gemcitabine is phosphorylated by an enzyme called deoxycytidine kinase.
• This process converts gemcitabine into its active forms: gemcitabine monophosphate, gemcitabine diphosphate, and gemcitabine triphosphate.
• Gemcitabine diphosphate acts by inhibiting ribonucleotide reductase, an enzyme crucial for the production of building blocks (nucleotides) required for DNA synthesis.
• On the other hand, gemcitabine triphosphate gets incorporated into the growing DNA chain, leading to the inhibition of DNA polymerase and preventing further DNA synthesis.
• In summary, gemcitabine exerts its effects by disrupting DNA synthesis through multiple mechanisms, ultimately interfering with the ability of cancer cells to divide and grow.

Distribution:

• Gemcitabine is widely distributed throughout the body and can reach various tissues, including ascitic fluid.
• The volume of distribution (V) depends on the duration of the infusion:
  • Infusions lasting less than 70 minutes: 50 liters per square meter of body surface area.
  • Longer infusion times (70 to 285 minutes): 370 liters per square meter of body surface area.

Protein Binding:

• Gemcitabine has negligible protein binding, meaning it does not strongly attach to proteins in the blood.

Metabolism:

• Inside the cells, gemcitabine is metabolized by enzymes called nucleoside kinases.
• This metabolism converts gemcitabine into its active forms: gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP), which are nucleoside metabolites responsible for its therapeutic effects.

Half-life Elimination:

• Gemcitabine:
  • For infusions lasting up to 70 minutes, the half-life ranges from 42 to 94 minutes.
  • For longer infusion times of 3 to 4 hours, the half-life extends to 4 to 10.5 hours.
  • The elimination half-life can be influenced by factors such as age and gender.
• Metabolite (gemcitabine triphosphate):
  • The terminal phase half-life of the active metabolite ranges from 1.7 to 19.4 hours.

Time to Peak, Plasma:

• The peak concentration of gemcitabine in the bloodstream occurs approximately 30 minutes after the completion of the infusion.

Excretion:

• Gemcitabine is primarily eliminated through urine, accounting for 92% to 98% of the administered dose. Most of it is excreted as an inactive uracil metabolite.
• Fecal excretion is minimal, accounting for less than 1% of the dose.

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International Brand Names of Gemcitabine:

• Gemzar
• Infugem
• ACT Gemcitabine
• Gemcitabine SUN
• Abine
• Abingem
• Bigemax
• Citabol
• Citafine
• Cytogem
• DBL
• Gembine
• Gembio
• Gemcetin
• Gemcibine
• Gemcikal
• Gemcit
• Gemcite
• Gemezar
• Gemflor
• Gemhope
• Gemita
• Gemmis
• Gemoxen
• Gemresec
• Gemtan
• Gemtavis
• Gemtero
• Gemtin
• Gemtra
• Gemtro
• Gemxit
• Gemzar
• Getanosan
• Gezt
• Gitrabin
• Oncogem
• Oncoril
• Pamigen
• Zarbin
• Zefei

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Gemcitabine Brand Names in Pakistan:

Gemcitabine Injection 1 G in Pakistan
Gemcit	Al-Habib Pharmaceuticals.
Gemcitabine	Novartis Pharma (Pak) Ltd
Gemita	Atco Laboratories Limited
Gemzar	Eli Lilly Pakistan (Pvt) Ltd.

 

Gemcitabine Injection 1 Gm in Pakistan
Oncogem	A. J. Mirza Pharma (Pvt) Ltd
Trugem	Pharmevo (Pvt) Ltd.

 

Gemcitabine Injection 100 Mg in Pakistan
Pamigen	Ferozsons Laboratoies Ltd.

 

Gemcitabine Injection 200 Mg in Pakistan
Gebina	Oncogene Pharmaceuticals Karachi
Gemcit	Al-Habib Pharmaceuticals.
Gemcitabine	Novartis Pharma (Pak) Ltd
Gemita	Atco Laboratories Limited
Gemzar	Eli Lilly Pakistan (Pvt) Ltd.
Oncogem	A. J. Mirza Pharma (Pvt) Ltd
Pamigen	Ferozsons Laboratoies Ltd.
Trugem	Pharmevo (Pvt) Ltd.

 

Gemcitabine Injection 1000 Mg in Pakistan
Gebina	Oncogene Pharmaceuticals Karachi