gemcitabine

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites, nucleoside analogues

High Alert

Pancreatic cancer (locally advanced or metastatic).
Inoperable locally advanced/metastatic non-small cell lung cancer (with cisplatin).
Metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy (unless anthracycline therapy contraindicated) (with paclitaxel).
Advanced ovarian cancer that has relapsed 6 mo after completion of platinum-based therapy (with carboplatin).

Interferes with DNA synthesis (cell-cycle phase-specific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Converted in cells to active diphosphate and triphosphate metabolites; these are excreted primarily by the kidneys.

Half-Life: 32–94 min.

(effect on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

Hypersensitivity;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

History of cardiovascular disease;
Hepatic or renal impairment (↑ risk of toxicity);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness in children not established.

CV: edema, ARRHYTHMIAS, CAPILLARY LEAK SYNDROME, CEREBROVASCULAR ACCIDENT, hypertension, MI

Derm: alopecia, rash

GI: ↑liver enzymes, diarrhea, nausea, stomatitis, vomiting, HEPATOTOXICITY

GU: hematuria, proteinuria, ↓fertility (males), HEMOLYTIC UREMIC SYNDROME, renal failure, thrombotic microangiopathy

Hemat: anemia, leukopenia, thrombocytopenia, thrombotic microangiopathy

Local: injection site reactions

Neuro: paresthesias, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Resp: dyspnea, ADULT RESPIRATORY DISTRESS SYNDROME, bronchospasm, pulmonary edema, PULMONARY FIBROSIS

Misc: flu-like symptoms, anaphylactoid reactions, fever

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
May ↓ antibody response to live virus vaccines and ↑ risk of adverse reactions.

Pancreatic Cancer

IV (Adults ): 1000 mg/m² once weekly for 7 wk, followed by a wk of rest, then on Days 1, 8, and 15 of each 28-day cycle.

Non-Small Cell Lung Cancer

IV (Adults ): 1000 mg/m² on Days 1, 8, and 15 of each 28-day cycle (cisplatin is also given on day 1) or 1250 mg/m² on Days 1 and 8 of each 21-day cycle (cisplatin is also given on Day 1).

Breast Cancer

IV (Adults ): 1250 mg/m² on Days 1 and 8 of each 21-day cycle (paclitaxel is also given on Day 1).

Ovarian Cancer

IV (Adults ): 1000 mg/m² on Days 1 and 8 of each 21-day cycle (carboplatin is also given on Day 1).

(Generic available)

Powder for injection: 200 mg/vial; 1 g/vial; 2 g/vial
Solution for injection: 200 mg/5.26 mL; 1 g/26.3 mL; 2 g/52.6 mL; 100 mg/mL

Monitor vital signs before and frequently during therapy.
Assess injection site during administration. Although gemcitabine is not a vesicant, it is an irritant, and local reactions may occur.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor intake and output, appetite, and nutritional intake. Mild to moderate nausea and vomiting occur frequently. Antiemetics may be used prophylactically.
Assess for signs and symptoms of capillary leak syndrome (severe hypotension, hypoalbuminemia, hemoconcentration). Discontinue therapy if symptoms occur.
Monitor respiratory status during therapy. Discontinue gemcitabine if unexplained dyspnea or other evidence of severe pulmonary toxicity occurs. May occur up to 2 wk after last dose.
Monitor for signs and symptoms of PRES (headache, seizure, lethargy, hypertension, confusion, blindness, and other visual and neurologic disturbances) during therapy. Confirm diagnosis of PRES with MRI. Discontinue gemcitabine if PRES develops during therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC, including differential and platelet count, before each dose. Dose guidelines are based on CBC. For single-agent use:If absolute granulocyte count is >1000 and platelet count is >100,000, full dose may be administered. If absolute granulocyte count is 500–999 or platelet count is 50,000–99,000, 75% of dose may be given. If absolute granulocyte count is <500 or platelet count is <50,000, withhold further doses. For gemcitabine with paclitaxel (breast cancer):If absolute granulocyte count is >1200 and platelet count is >75,000, full dose may be administered. If absolute granulocyte count is 1000–1199 or platelet count is 50,000–75,000, 75% of dose may be given. If absolute granulocyte count is 700–999 or platelet count is ≥50,000, 50% of dose may be given. If absolute granulocyte count is <700 or platelet count is <50,000, withhold further doses. For gemcitabine with carboplatin (ovarian cancer):If absolute granulocyte count is >1500 and platelet count is >100,000, full dose may be administered. If the absolute granulocyte count is 1000–1499 or platelet count is 75,000–99,000, 75% of dose may be given. If the absolute granulocyte count is <1000 or the platelet count is <75,000, withhold further doses.
- Monitor serum creatinine, potassium, calcium, and magnesium in patients taking cisplatin with gemcitabine.
- Monitor hepatic and renal function before and periodically during therapy. May cause transient ↑ in serum AST, ALT, alkaline phosphatase, and bilirubin concentrations. Discontinue gemcitabine for severe hepatic toxicity or hemolytic-uremic syndrome.
- May also cause ↑ BUN and serum creatinine concentrations, proteinuria, and hematuria.

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Intermittent Infusion: Reconstitution: To reconstitute, add 5 mL of 0.9% NaCl without preservatives to 200-mg vial, 25 mL of 0.9% NaCl to the 1-g vial of gemcitabine or 50 mL to the 2-g vial. Concentration of 38 mg/mL. Incomplete dissolution may result in concentrations greater than 40 mg/mL.Diluent: May be further diluted with 0.9% NaCl. Solution is colorless to light straw color. Do not administer solutions that are discolored or contain particulate matter. Solution is stable for 24 hr at room temperature. Discard unused portions. Do not refrigerate; crystallization may occur.
Rate: Administer dose over 30 min. If 2 bags required, infuse total of both bags over 30 min. Infusions longer than 60 min have a greater incidence of toxicity.

Explain purpose of gemcitabine to patient.
Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patient should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis pain may require management with opioid analgesics.
Instruct patient to notify health care professional if flu-like symptoms (fever, anorexia, headache, cough, chills, myalgia), swelling of feet or legs, signs and symptoms of pulmonary toxicity (shortness of breath, wheezing, cough), hemolytic-uremic syndrome (changes in color or volume of urine output, increased bruising or bleeding), or hepatic toxicity (jaundice, pain/tenderness in right upper abdominal quadrant) occur.
Discuss with patient the possibility of hair loss. Explore methods of coping.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo after final dose and to avoid breastfeeding during and for at least 1 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose. May cause male infertility.
Emphasize the need for periodic lab tests to monitor for side effects.

Palliative, symptomatic improvement in patients with pancreatic cancer.
Decrease in size and spread of malignancy in lung, ovarian, and breast cancer.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆