Gemcitabine

Dosage Forms

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); gemcitabine hydrochloride 2,200 mg/220 mL in NaCl 0.9% (220 mL); gemcitabine hydrochloride 2,000 mg/200 mL in NaCl 0.9% (200 mL); gemcitabine hydrochloride 1,300 mg/130 mL in NaCl 0.9% (130 mL); gemcitabine hydrochloride 1,400 mg/140 mL in NaCl 0.9% (140 mL); gemcitabine hydrochloride 1,500 mg/150 mL in NaCl 0.9% (150 mL); gemcitabine hydrochloride 1,600 mg/160 mL in NaCl 0.9% (160 mL); gemcitabine hydrochloride 1,700 mg/170 mL in NaCl 0.9% (170 mL); gemcitabine hydrochloride 1,800 mg/180 mL in NaCl 0.9% (180 mL) [latex free]

Infugem: gemcitabine hydrochloride 1,900 mg/190 mL in NaCl 0.9% (190 mL)

Solution Reconstituted, Intravenous:

Gemzar: 200 mg (1 ea [DSC]); 1 g (1 ea [DSC])

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); 2 g (1 ea [DSC])

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

Widely distributed into tissues; present in ascitic fluid; V_d: Infusions <70 minutes: 50 L/m²; Long infusion times (70 to 285 minutes): 370 L/m²

Metabolism

Metabolized intracellularly by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside metabolites

Excretion

Urine (92% to 98%; primarily as inactive uracil metabolite); feces (<1%)

Time to Peak

30 minutes after completion of infusion

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

Protein Binding

Negligible

Use in Specific Populations

Special Populations: Elderly

The lower clearance in geriatric patients results in higher concentrations of gemcitabine for any given dose.

Special Populations: Gender

Gemcitabine clearance is lower and the half-life is longer in females (compared with males).

Use: Labeled Indications

Breast cancer (metastatic): First-line treatment of metastatic breast cancer (in combination with paclitaxel) after failure of adjuvant chemotherapy that contained an anthracycline (unless anthracyclines are contraindicated).

Non-small cell lung cancer (inoperable, locally advanced, or metastatic): First-line treatment (in combination with cisplatin) of inoperable, locally advanced (stage IIIA or IIIB) or metastatic (stage IV) non-small cell lung cancer (NSCLC).

Ovarian cancer (advanced): Treatment of advanced ovarian cancer (in combination with carboplatin) that has relapsed at least 6 months following completion of platinum-based chemotherapy.

Pancreatic cancer (locally advanced or metastatic): First-line treatment of locally advanced (nonresectable stage II or III) or metastatic (stage IV) pancreatic adenocarcinoma. Gemcitabine is indicated for patients previously treated with fluorouracil.

Guideline recommendations:

Metastatic pancreatic cancer: American Society of Clinical Oncology (ASCO) guidelines for metastatic pancreatic cancer (ASCO [Sohal 2018]) recommend gemcitabine (in combination with paclitaxel [protein bound]) as first-line therapy in patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, a relatively favorable comorbidity profile, a preference for relatively aggressive therapy, and a suitable support system. First-line therapy with single-agent gemcitabine is recommended in patients with ECOG performance status of 2 or a comorbidity profile prohibiting more aggressive therapy when there is a preference for cancer-directed therapy; capecitabine or erlotinib (added to gemcitabine) may also be offered in this situation. Gemcitabine (in combination with paclitaxel [protein bound]) may be utilized as second-line therapy in patients who received first-line FOLFIRINOX therapy, have an ECOG performance status of 0 or 1, have a relatively favorable comorbidity profile, a preference for aggressive therapy, and a suitable support system. Second-line therapy with gemcitabine (alone) may also be considered as an option in patients with ECOG performance status of 2 or a comorbidity profile prohibiting more aggressive regimens when there is a preference to pursue cancer-directed therapy.

Locally advanced, unresectable pancreatic cancer: According to the ASCO guidelines for locally advanced, unresectable pancreatic cancer (ASCO [Balaban 2016]), induction with 6 months of initial systemic therapy (with a combination regimen) is generally recommended, although there is not enough evidence to encourage one regimen over another, and gemcitabine-based therapies recommended in the metastatic setting have not been evaluated in randomized controlled studies for locally advanced unresectable pancreatic cancer. If disease progression occurs, treatment according to guidelines for metastatic pancreatic cancer should be offered.

Use: Off Label

Bladder cancer (advanced or metastatic)ayes

Data from a large phase 3, randomized study support the use of gemcitabine (in combination with cisplatin) for the treatment of advanced or metastatic bladder cancer von der Maase 2000. Data from a phase 2/3 study in patients with advanced bladder cancer who were ineligible to receive cisplatin support the use of gemcitabine (in combination with carboplatin) in this population De Santis 2012.

Based on the treatment of non-metastatic muscle-invasive bladder cancer American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guideline, gemcitabine (in combination with cisplatin) may be utilized as neoadjuvant therapy in the management of muscle-invasive bladder cancer.

Bladder cancer (transitional cell, refractory)b

Data from a small phase 2 study support the use of intravesicular gemcitabine for the treatment of transitional cell carcinoma of the bladder in patients who are intolerant of or with disease refractory to intravesicular BCG instillation Dalbagni 2006.

Cervical cancer (recurrent or persistent)b

Data from a randomized, phase 3 study comparing gemcitabine (in combination with cisplatin) to 3 other cisplatin-containing doublet regimens support the use of gemcitabine for the treatment of advanced, recurrent or persistent cervical carcinoma Monk 2009. Data from 2 small phase 2 studies also support the use of gemcitabine (in combination with cisplatin) for the treatment of advanced, persistent, or recurrent cervical cancer Brewer 2006, Burnett 2000. Data from a small phase 2 study in patients with recurrent or persistent non-squamous cell cervical cancer supports the use of gemcitabine as a single agent Schilder 2005.

Ewing sarcoma (refractory)c

Data from a small retrospective study (in patients ages 8 to 23 years) suggest that gemcitabine (in combination with docetaxel) may be beneficial for the treatment of refractory Ewing sarcoma Navid 2008.

Head and neck cancer: nasopharyngeal (advanced or metastatic)b

Data from a small phase 2 study support the use of gemcitabine (as a single agent) in the management of advanced nasopharyngeal carcinoma after failure of platinum-based therapy Zhang 2008. Data from another phase 2 study support the use of gemcitabine (in combination with vinorelbine) as salvage therapy in patients who had previously received platinum-based therapy for the treatment of metastatic nasopharyngeal carcinoma Chen 2012.

Hepatobiliary cancer (advanced)a

Data from a large randomized, phase 3 study support the use of gemcitabine (in combination with cisplatin) in the treatment of unresectable, recurrent or metastatic biliary tract cancers, including cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma Valle 2010. Data from 2 phase 2 studies support the use of gemcitabine (in combination with either oxaliplatin or capecitabine) for the treatment of advanced biliary tract cancers André 2004, Knox 2005.

Hodgkin lymphoma (relapsed)b

Survival data from a phase 1/2 study in adults support the use of gemcitabine (in combination with vinorelbine and doxorubicin liposomal) as a salvage regimen for relapsed or refractory Hodgkin lymphoma Bartlett 2007. Data from a study (in patients 17 years of age and older) support the use of gemcitabine (in combination with ifosfamide, mesna, vinorelbine, and prednisolone) as salvage induction therapy for relapsed or refractory Hodgkin lymphoma Santoro 2007.

Malignant pleural mesotheliomab

Data from 2 multicenter, phase 2 studies support the use of gemcitabine (in combination with cisplatin) in the management of malignant pleural mesothelioma Nowak 2002, van Haarst 2002.

Non-Hodgkin lymphoma (relapsed/refractory)b

Data from a phase 2 study support the use of gemcitabine (in combination with cisplatin and dexamethasone) for the treatment of relapsed or refractory diffuse large B cell non-Hodgkin lymphoma Crump 2004. Data from a phase 2 study support the use of gemcitabine (in combination with oxaliplatin and rituximab) as salvage therapy for relapsed or refractory diffuse large B cell non-Hodgkin lymphoma Lopez 2008.

Osteosarcoma (refractory)c

Data from a small retrospective study (in patients ages 8 to 23 years) suggest that gemcitabine (in combination with docetaxel) may be beneficial for the treatment of refractory osteosarcoma Navid 2008. Data from a small phase 2 study in soft tissue and bone sarcomas (which included some osteosarcomas) support the use of gemcitabine (as a single agent) in the treatment of refractory osteosarcoma Merimsky 2000.

Pancreatic cancer, potentially curable (adjuvant therapy)ayes

Data from a randomized, multicenter, phase 3 study support the use of gemcitabine (in combination with capecitabine) in the adjuvant treatment of completely resected pancreatic adenocarcinoma Neoptolemos 2017. Data from a multicenter, randomized, phase 3 study (including long-term follow-up) support the use of gemcitabine (as a single agent) for the treatment of resected pancreatic cancer Oettle 2007, Oettle 2013.

According to the ASCO guidelines for potentially curable pancreatic cancer, while first-line adjuvant therapy with another regimen is preferred, gemcitabine (in combination with capecitabine) or single-agent gemcitabine are adjuvant therapy options (in the absence of contraindications) if toxicity or tolerance are concerns with the preferred therapy.

Renal carcinoma (metastatic)b

Data from a multicenter, phase 2 study support the use of gemcitabine (in combination with either cisplatin or carboplatin) for the treatment of metastatic collecting duct renal carcinoma Oudard 2007.

Small cell lung cancer (refractory or relapsed)b

A small phase 2 study demonstrated modest activity but limited toxicity and supports the use of gemcitabine (as a single agent) in the treatment of relapsed or refractory small cell lung cancer Masters 2003.

Soft tissue sarcoma (advanced)b

Data from a phase 2 study support the use of gemcitabine (in combination with docetaxel) in the treatment of metastatic soft tissue sarcoma Maki 2007. Data from a phase 2 study support the use of gemcitabine (in combination with vinorelbine) in the treatment of advanced soft tissue sarcomas Dileo 2007. A retrospective review in patients with bone and soft tissue sarcoma suggest the utility of using gemcitabine (in combination with docetaxel) for the treatment of soft-tissue sarcoma Leu 2004.

Testicular cancer (refractory germ cell)b

Data from 3 phase 2 studies support the use of gemcitabine (in combination with oxaliplatin) in the treatment of cisplatin-refractory germ cell tumors DeGiorgi 2006, Kollmannsberger 2004, Pectasides 2004. Data from a small phase 2 study support the use of gemcitabine (in combination with paclitaxel) in the treatment of refractory germ cell tumors Hinton 2002. Additionally, a phase 2 study support the use of gemcitabine (in combination with oxaliplatin and paclitaxel) for the treatment of refractory or relapsed (multiply relapsed) germ cell tumors Bokemeyer 2008.

Thymic malignancies (refractory)c

Preliminary data from a small phase 2 study suggest that gemcitabine (in combination with capecitabine) has activity in the treatment of refractory thymic malignancies Palmieri 2010.

Unknown-primary carcinomab

Data from a phase 2 study support the use of gemcitabine (in combination with docetaxel) in the management of unknown primary carcinoma Pouessel 2004. Data from 2 small studies demonstrated activity with the use of gemcitabine (in combination with cisplatin) for management of unknown primary carcinoma Culine 2003, Gross-Goupil 2012.

Uterine cancerb

Data from a phase 2 study support the use of fixed-dose rate gemcitabine (in combination with docetaxel) for the treatment of metastatic uterine leiomyosarcoma Hensley 2008. Data from a phase 2 study support the use of gemcitabine as a single agent for management of recurrent or persistent uterine leiomyosarcoma in patients who had received prior chemotherapy Look 2004.

Contraindications

Known hypersensitivity to gemcitabine or any component of the formulation

Dosage and Administration

Dosing: Adult

Note: Prolongation of the infusion duration >60 minutes and administration more frequently than once weekly have been shown to increase toxicity. 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).

Bladder cancer (off-label use):

Advanced or metastatic: IV: 1,000 mg/m² over 30 to 60 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with cisplatin) (von der Maase 2000) or 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) until disease progression or unacceptable toxicity (De Santis 2012).

Transitional cell carcinoma (refractory): 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 (Dalbagni 2006).

Breast cancer (metastatic): IV: 1,250 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with paclitaxel) until disease progression or unacceptable toxicity (Albain 2008) or

Off-label dosing (as a single-agent): 800 mg/m² over 30 minutes days 1, 8, and 15 of a 28-day treatment cycle (Carmichael 1995).

Cervical cancer, recurrent or persistent (off-label use): IV: 1,000 mg/m² days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Monk 2009) or 1,250 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Burnett 2000) or 800 mg/m² over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (as a single-agent) (Schilder 2005) or 800 mg/m² days 1 and 8; repeat cycle every 28 days (in combination with cisplatin) (Brewer 2006).

Head and neck cancer: nasopharyngeal, advanced or metastatic (off-label use): IV: 1,000 mg/m² over 30 minutes days 1, 8, and 15 every 28 days (Zhang 2008) or 1,000 mg/m² over 30 minutes days 1 and 8 every 21 days (in combination with vinorelbine) (Chen 2012).

Hepatobiliary cancer, advanced (off-label use): IV: 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) (Valle 2010) or 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with capecitabine) (Knox 2005) or 1,000 mg/m² infused at 10 mg/m²/minute every 2 weeks (in combination with oxaliplatin) (Andre 2004).

Hodgkin lymphoma, relapsed (off-label use): IV: 1,000 mg/m² (800 mg/m² for post-transplant patients) over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine and doxorubicin liposomal) (Bartlett 2007) or 800 mg/m² days 1 and 4; repeat cycle every 21 days (in combination with ifosfamide, mesna, vinorelbine, and prednisolone) (Santoro 2007).

Malignant pleural mesothelioma (off-label use; in combination with cisplatin): IV: 1,000 mg/m² over 30 minutes days 1, 8 and 15 every 28 days for up to 6 cycles (Nowak 2002) or 1,250 mg/m² over 30 minutes days 1 and 8 every 21 days for up to 6 cycles (van Haarst 2002).

Non-Hodgkin lymphoma, refractory (off-label use): IV: 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin and dexamethasone) (Crump 2004) or 1,000 mg/m² every 15 to 21 days (in combination with oxaliplatin and rituximab) (Lopez 2008).

Non-small cell lung cancer (inoperable, locally advanced, or metastatic): IV: 1,000 mg/m² over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with cisplatin) or 1,250 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with cisplatin) or

Off-label dosing/combinations: 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) for up to 4 cycles (Grønberg 2009) or 1,000 mg/m² over 30 minutes days 1, 8, and 15; repeat cycle every 28 days (in combination with carboplatin) for up to 4 cycles (Danson 2003) or 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) for 8 cycles (Pujol 2005) or 1,000 mg/m² days 1, 8, and 15; repeat cycle every 28 days (in combination with vinorelbine) for 6 cycles (Greco 2007).

Ovarian cancer (advanced): IV: 1,000 mg/m² over 30 minutes days 1 and 8; repeat cycle every 21 days (in combination with carboplatin) (Pfisterer 2005) or

Off-label dosing (as a single agent): 1,000 mg/m² over 30 to 60 minutes days 1 and 8; repeat cycle every 21 days (Mutch 2007).

Pancreatic cancer (locally advanced or metastatic): IV: Initial: 1,000 mg/m² over 30 minutes once weekly for 7 weeks followed by 1 week rest; then administer on days 1, 8, and 15 every 28 days (Burris 1997) or

Off-label dosing/combinations: 1,000 mg/m² days 1, 8, and 15 every 28 days (in combination with paclitaxel [protein bound]) (Von Hoff 2013) or 1,000 mg/m² over 30 minutes days 1, 8, and 15 every 28 days (in combination with capecitabine) (Cunningham 2009) or 1,000 mg/m² over 30 minutes weekly for up to 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks (in combination with erlotinib) (Moore 2007) or 1,000 mg/m² over 30 minutes days 1 and 15 every 28 days (in combination with cisplatin) (Heinemann 2006) or 1,000 mg/m² infused at 10 mg/m²/minute every 14 days (in combination with oxaliplatin) (Louvet 2005).

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 (ASCO [Khorana 2019]).

IV:

Combination regimen: 1,000 mg/m² on days 1, 8, and 15 every 28 days (in combination with capecitabine) for 6 cycles beginning within 12 weeks of resection (Neoptolemos 2017).

Single-agent therapy: 1,000 mg/m² on days 1, 8, and 15 every 28 days for 6 cycles (Oettle 2007; Oettle 2013).

Sarcomas (off-label uses): IV:

Ewing sarcoma, refractory: 675 mg/m² over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid 2008).

Osteosarcoma, refractory: 675 mg/m² over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Navid 2008) or 1,000 mg/m² weekly for 7 weeks followed by 1 week rest; then weekly for 3 weeks out of every 4 weeks (Merimsky 2000).

Soft tissue sarcoma, advanced: 800 mg/m² over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with vinorelbine) (Dileo 2007) or 675 mg/m² over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Leu 2004) or 900 mg/m² over 90 minutes days 1 and 8; repeat cycle every 21 days (in combination with docetaxel) (Maki 2007).

Small cell lung cancer, refractory or relapsed (off-label use): IV: 1,000 to 1,250 mg/m² over 30 minutes days 1, 8, and 15 every 28 days (as a single agent) (Masters 2003).

Testicular cancer, refractory germ cell (off-label use): IV: 1,000 to 1,250 mg/m² over 30 minutes days 1 and 8 every 21 days (in combination with oxaliplatin) (DeGiorgi 2006; Kollmannsberger 2004; Pectasides 2004) or 1,000 mg/m² over 30 minutes days 1, 8, and 15 every 28 days for up to 6 cycles (in combination with paclitaxel) (Hinton 2002) or 800 mg/m² over 30 minutes days 1 and 8 every 21 days (in combination with oxaliplatin and paclitaxel) (Bokemeyer 2008).

Unknown-primary, adenocarcinoma (off-label use): IV: 1,250 mg/m² days 1 and 8 every 21 days (in combination with cisplatin) (Culine 2003; Gross-Goupil 2012) or 1,000 mg/m² over 30 minutes days 1 and 8 every 21 days for up to 6 cycles (in combination with docetaxel) (Pouessel 2004).

Uterine cancer (off-label use): IV: 900 mg/m² over 90 minutes days 1 and 8 every 21 days (in combination with docetaxel) (Hensley 2008) or 1,000 mg/m² over 30 minutes days 1, 8, and 15 every 28 days (Look 2004).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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 (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting (Basch 2011; Dupuis 2013; Roila 2010).

Hodgkin lymphoma, refractory or relapsed: Limited data available:

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 (Cole 2009)

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 (Suyani 2011) or 800 mg/m²/dose on days 1 and 4 (in combination with ifosfamide and vinorelbine); repeat cycle every 21 days (Santoro 2007)

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 (Mora 2009; Navid 2008) or 1,000 mg/m²/dose over 30 minutes on days 1 and 8 (in combination with oxaliplatin and irinotecan); repeat cycle every 28 days (Hartmann 2011)

Solid tumors, refractory or relapsed: 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 (Hartmann 2011) or 1,000 mg/m²/dose over 100 minutes on day 1 (in combination with oxaliplatin); repeat cycle every 14 days (Geoerger 2011)

Note: Dosage reductions for toxicity (Geoerger 2011): 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

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 (Einhorn 1999)

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 granulocyte count (AGC) ≥1,500/mm³ and platelet count ≥100,000/mm³: Administer 100% of full dose

AGC <1,500/mm³ or platelet count <100,000/mm³: Hold dose

Day 8:

AGC ≥1,200/mm³ and platelet count >75,000/mm³: Administer 100% of full dose

AGC 1,000 to 1,199/mm³ or platelet count 50,000 to 75,000/mm³: Administer 75% of full dose

AGC 700 to 999/mm³ and platelet count ≥50,000/mm³: Administer 50% of full dose

AGC <700/mm³ or platelet count <50,000/mm³: Hold dose

Non-small cell lung cancer (cisplatin dosage may also require adjustment):

AGC ≥1,000/mm³ and platelet count ≥100,000/mm³: Administer 100% of full dose

AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³: Administer 75% of full dose

AGC <500/mm³ or platelet count <50,000/mm³: Hold dose

Ovarian cancer:

Day 1:

AGC ≥1,500/mm³ and platelet count ≥100,000/mm³: Administer 100% of full dose

AGC <1,500/mm³ or platelet count <100,000/mm³: Delay treatment cycle

Day 8:

AGC ≥1,500/mm³ and platelet count ≥100,000/mm³: Administer 100% of full dose

AGC 1,000 to 1,499/mm³ or platelet count 75,000 to 99,999/mm³: Administer 50% of full dose

AGC <1,000/mm³ or platelet count <75,000/mm³: Hold dose

Hematologic toxicity in previous cycle (dosing adjustment for subsequent cycles):

Initial occurrence: 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 gemcitabine to 800 mg/m² on days 1 and 8

Subsequent occurrence: 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 gemcitabine to 800 mg/m² and administer on day 1 only

Pancreatic cancer:

AGC ≥1,000/mm³ and platelet count ≥100,000/mm³: Administer 100% of full dose

AGC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³: Administer 75% of full dose

AGC <500/mm³ or platelet count <50,000/mm³: Hold dose

Dosing: Adjustment for Toxicity

Note: If administering in combination, concomitant chemotherapy agents may also require treatment interruption, dosage reduction, and/or discontinuation.

Nonhematologic toxicity (all indications):

Withhold or decrease gemcitabine dose by 50% for severe (grade 3 or 4) nonhematologic toxicity until resolved (excludes nausea, vomiting, or alopecia [no dose modifications are recommended for these toxicities]).

Permanently discontinue gemcitabine for any of the following: Unexplained dyspnea (with or without bronchospasm), or evidence of severe pulmonary toxicity, severe hepatotoxicity or severe liver injury, hemolytic uremic syndrome or severe renal impairment, capillary leak syndrome, posterior reversible encephalopathy syndrome.

Hematologic toxicity:

Breast cancer:

Day 1:

ANC ≥1,500/mm³ and platelet count ≥100,000/mm³: Administer 100% of full gemcitabine dose.

ANC <1,500/mm³ or platelet count <100,000/mm³: Hold gemcitabine dose.

Day 8:

ANC ≥1,200/mm³ and platelet count >75,000/mm³: Administer 100% of full gemcitabine dose.

ANC 1,000 to 1,199/mm³ or platelet count 50,000 to 75,000/mm³: Administer 75% of full gemcitabine dose.

ANC 700 to 999/mm³ and platelet count ≥50,000/mm³: Administer 50% of full gemcitabine dose.

ANC <700/mm³ or platelet count <50,000/mm³: Hold gemcitabine 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 gemcitabine dose.

ANC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³: Administer 75% of full gemcitabine dose.

ANC <500/mm³ or platelet count <50,000/mm³: Hold gemcitabine dose.

Ovarian cancer:

Day 1:

ANC ≥1,500/mm³ and platelet count ≥100,000/mm³: Administer 100% of full gemcitabine 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 gemcitabine dose.

ANC 1,000 to 1,499/mm³ or platelet count 75,000 to 99,999/mm³: Administer 50% of full gemcitabine dose.

ANC <1,000/mm³ or platelet count <75,000/mm³: Hold gemcitabine 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, neutropenic fever, platelet count <25,000/mm³, or cycle delay >1 week due to toxicity: Permanently reduce gemcitabine dose to 800 mg/m² on days 1 and 8.

Subsequent occurrence (after initial dose reduction): 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 dose to 800 mg/m² and administer on day 1 only.

Pancreatic cancer (locally advanced or metastatic):

ANC ≥1,000/mm³ and platelet count ≥100,000/mm³: Administer 100% of full gemcitabine dose.

ANC 500 to 999/mm³ or platelet count 50,000 to 99,999/mm³: Administer 75% of full gemcitabine dose.

ANC <500/mm³ or platelet count <50,000/mm³: Hold gemcitabine dose.

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Reconstitution

Lyophilized powder: Reconstitute lyophilized powder with preservative free NS; add 5 mL to the 200 mg vial, add 25 mL to the 1,000 mg vial, or add 50 mL to the 2,000 mg vial, resulting in a reconstituted concentration of 38 mg/mL.

Concentrated solution for injection (vial): Gemcitabine solution for injection may be available in various concentrations; verify product carefully prior to admixture to ensure appropriate dose preparation.

Reconstituted solutions and concentrated solution for injection in a vial must be further diluted prior to administration. Further dilute reconstituted lyophilized powder or concentrated solution for injection in NS for infusion; to a minimum final concentration of at least 0.1 mg/mL.

Premixed infusion solutions: Select the premixed bag(s) that allow for a variance of ≤5% of the BSA-based calculated dose. Premixed bags are ready to use and do not require further preparation. Do not dilute prior to use. Do not remove or add medications. After removing bag from overwrap, check for leaks by firmly squeezing the inner bag (discard if leaks are found). Do not use premixed infusions bags for patients requiring <1,200 mg/dose (select a different formulation).

Administration

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 (Ko 2006; Tempero 2003). Patients who receive gemcitabine FDR experience more grade 3/4 hematologic toxicity (Ko 2006; Poplin 2009).

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 (Addeo 2010; Dalbaghi 2006)

Storage

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).

Drug Interactions

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. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bleomycin: Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Consider therapy modification

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. 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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fluorouracil (Systemic): Gemcitabine may increase the serum concentration of Fluorouracil (Systemic). Monitor therapy

Fluorouracil (Topical): Gemcitabine may increase the serum concentration of Fluorouracil (Topical). Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

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. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

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. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

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. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Warfarin: Gemcitabine may enhance the anticoagulant effect of Warfarin. Monitor therapy

Adverse Reactions

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

>10%:

Cardiovascular: Peripheral edema (20%), edema (≤13%)

Central nervous system: Drowsiness (11%)

Dermatologic: Skin rash (30%), alopecia (15%)

Gastrointestinal: Nausea and vomiting (69%), diarrhea (19%), stomatitis (11%; grade 3: <1%)

Genitourinary: Proteinuria (45%), hematuria (35%)

Hematologic & oncologic: Anemia (68%; grade 3: 7%; grade 4: 1%), neutropenia (63%; grade 3: 19%; grade 4: 6%), thrombocytopenia (24%; grade 3: 4%; grade 4: 1%), hemorrhage (17%; grade 3: <1%; grade 4: <1%)

Hepatic: Increased serum alanine aminotransferase (68%), increased serum aspartate aminotransferase (67%), increased serum alkaline phosphatase (55%), hyperbilirubinemia (13%)

Infection: Infection (16%)

Renal: Increased blood urea nitrogen (16%)

Respiratory: Dyspnea (23%), flu-like symptoms (19%)

Miscellaneous: Fever (41%)

1% to 10%:

Central nervous system: Paresthesia (10%)

Local: Injection site reaction (4%)

Renal: Increased serum creatinine (8%)

Respiratory: Bronchospasm (<2%)

Frequency not defined:

Hypersensitivity: Nonimmune anaphylaxis

<1%, postmarketing, and/or case reports (reported with single-agent use or with combination therapy): Acute myocardial infarction, acute respiratory distress syndrome, bullous skin disease, capillary leak syndrome, cardiac arrhythmia, cardiac failure, cellulitis (including pseudocellulitis), cerebrovascular accident (Kuenen 2002), desquamation, eosinophilic pneumonitis, gangrene of skin and/or subcutaneous tissues, hemolytic-uremic syndrome, hepatic failure, hepatic sinusoidal obstruction syndrome, hepatotoxicity, interstitial pneumonitis, petechia (Nishijima 2013; Zupancic 2007), pruritus (Curtis 2016), pulmonary edema, pulmonary fibrosis, radiation recall phenomenon, renal failure syndrome, respiratory failure, reversible posterior leukoencephalopathy syndrome, sepsis, severe dermatological reaction, supraventricular cardiac arrhythmia, thrombotic microangiopathy, thrombotic thrombocytopenic purpura (Nishijima 2013; Zupancic 2007), vasculitis (peripheral)

Warnings/Precautions

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. Monitor blood counts. Hematologic toxicity may require treatment interruption, dosage reduction, and/or discontinuation.
• Capillary leak syndrome: Capillary leak syndrome (CLS) with serious consequences has been reported, both with single-agent gemcitabine and with combination chemotherapy; permanently discontinue gemcitabine if CLS develops.
• Hemolytic uremic syndrome: Hemolytic uremic syndrome (HUS) has been reported; may lead to renal failure and dialysis (including fatalities). Most fatal cases of renal failure were due to HUS. Thrombotic microangiopathy other than HUS has also been reported. Monitor renal function at baseline and periodically during treatment. Assess for HUS in patients who develop anemia with microangiopathic hemolysis, elevation of bilirubin or lactate dehydrogenase, reticulocytosis, severe thrombocytopenia, and/or renal failure (increased serum creatinine or BUN). Permanently discontinue if HUS or severe renal impairment occurs; renal 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. Monitor hepatic function at baseline and periodically during treatment; consider dose adjustments with elevated bilirubin; permanently discontinue if severe hepatotoxicity develops.
• 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. If PRES diagnosis is confirmed (by MRI), permanently discontinue gemcitabine therapy.
• Pulmonary toxicity: Pulmonary toxicity, including adult respiratory distress syndrome, interstitial pneumonitis, pulmonary edema, and pulmonary fibrosis, has been observed; may lead to respiratory failure (some fatal) despite gemcitabine discontinuation. The onset of pulmonary toxicity symptoms may be delayed up to 2 weeks beyond the last gemcitabine dose. Permanently discontinue for unexplained dyspnea (with or without bronchospasm) or evidence of severe pulmonary toxicity.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: In some studies, higher rates of grades 3 and 4 neutropenia and thrombocytopenia have been observed in patients ≥65 years of age (compared to younger patients).
• 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; 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 >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).
• Multiple concentrations: Gemcitabine is available in multiple formulations and concentrations; verify product and concentration prior to admixture to assure appropriate dose preparation.

Monitoring Parameters

CBC with differential and platelet count (prior to each dose); hepatic and renal function (prior to initiation of therapy and periodically, thereafter); monitor electrolytes, including potassium, magnesium, and calcium (when in combination therapy with cisplatin); pregnancy test (prior to treatment initiation) in females of reproductive potential; monitor pulmonary function. Monitor for signs/symptoms of capillary leak syndrome, hemolytic uremic syndrome, pulmonary toxicity, and posterior reversible encephalopathy syndrome.

Pregnancy

Pregnancy Considerations

Based on the mechanism of action and on findings from animal reproduction studies, gemcitabine may cause fetal harm if administered during pregnancy.

Information related to the use of gemcitabine in pregnancy is limited (Lubner 2011; Wiesweg 2014).

Verify pregnancy status (with pregnancy test) prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for 6 months after the final gemcitabine dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the final gemcitabine dose.

A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).

Patient Education

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Flu-like symptoms
• Nausea
• Vomiting
• Diarrhea
• Lack of appetite
• Constipation
• Mouth sores
• Mouth irritation
• Hair loss
• Loss of strength and energy
• Fatigue

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Capillary leak syndrome like abnormal heartbeat; chest pain; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; unable to pass urine or change in amount of urine passed; blood in the urine.
• Posterior reversible encephalopathy syndrome like confusion, not alert, vision changes, seizures, or severe headache.
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
• High blood sugar like confusion, feeling sleepy, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.
• Hemolytic-uremic syndrome like unable to pass urine; loss of strength and energy; signs of bleeding or bruising; fever; or swelling of the face, hands, feet, or body.
• Difficulty breathing
• Severe dizziness
• Passing out
• Burning or numbness feeling
• Edema
• Severe injection site burning, redness, edema, pain, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.