General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
jem-site-a-been

Trade Name(s)

• Avgemsi
• Gemzar

Ther. Class.

antineoplastics

Pharm. Class.

antimetabolites

nucleoside analogues

Indications

• 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).

Action

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

Therapeutic Effect(s):

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

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

Half-life: 32–94 min.

TIME/ACTION PROFILE ( effect on blood counts)

Contraindication/Precautions

Contraindicated in:

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

Use Cautiously in:

• History of cardiovascular disease;
• Renal impairment;
• Hepatic impairment;
• Rep:   Women of reproductive potential and men with female partners of reproductive potential;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

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

Derm: alopecia, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

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

GU: hematuria, proteinuria, ↓ fertility (men), 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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

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

Route/Dosage

Pancreatic Cancer

IV (Adults): 1000 mg/m²  once weekly for 7 wk, followed by a week of rest, and then 1000 mg/m²  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).

Availability (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

Assessment

• Monitor vital signs before and frequently during therapy.
• 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 ↑ 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/symptoms of capillary leak syndrome (severe hypotension, hypoalbuminemia, hemoconcentration).  If capillary leak syndrome symptoms occur,  discontinue gemcitabine.
• Monitor respiratory status during therapy.  If unexplained dyspnea or other evidence of severe pulmonary toxicity occurs,  discontinue gemcitabine. May occur up to 2 wk after last dose.
• Monitor for signs/symptoms of PRES (headache, seizure, lethargy, hypertension, confusion, blindness, other visual and neurologic disturbances) during therapy. Confirm diagnosis of PRES with MRI.  If PRES occurs,  discontinue gemcitabine.
• Monitor for signs/symptoms of exanthematous pustulosis (itching; burning; fever; nonfollicular pustular rash on a red base in the armpits, groin, behind the knees, on the inner elbows, or on the face that spreads to other areas), which can occur within 1–2 days of taking the medication but can take up to 2 wk.  If exanthematous pustulosis occurs, discontinue gemcitabine.
• Monitor for signs/symptoms of severe cutaneous adverse reactions (prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, lymphadenopathy), including DRESS, SJS, and TEN.  If severe cutaneous adverse reaction suspected,  hold gemcitabine until etiology is determined.  If severe cutaneous adverse reaction confirmed, permanently discontinue gemcitabine.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

Monitor CBC with differential before each dose.  For single-agent use:   If ANC >1000 cells/mm³  and platelets >100,000 cells/mm³ ,  administer full dose.  If ANC 500–999 cells/mm³  or platelets 50,000–99,000 cells/mm³ ,  administer 75% of dose.  If ANC <500 cells/mm³  or platelets <50,000 cells/mm³ ,  hold gemcitabine.  For gemcitabine with paclitaxel (breast cancer):   If ANC >1200 cells/mm³  and platelets >75,000 cells/mm³ ,  administer full dose.  If ANC 1000–1199 cells/mm³  or platelets 50,000–75,000 cells/mm³ ,  administer 75% of dose.  If ANC 700–999 cells/mm³  or platelets ≥50,000 cells/mm³ ,  administer 50% of dose.  If ANC <700 cells/mm³  or platelets <50,000 cells/mm³ ,  hold gemcitabine.  For gemcitabine with carboplatin (ovarian cancer):  If ANC >1500 cells/mm³  and platelets >100,000 cells/mm³ ,  administer full dose.  If ANC 1000–1499 cells/mm³  or platelets 75,000–99,000 cells/mm³ ,  administer 75% of dose.  If ANC <1000 cells/mm³  or platelets <75,000 cells/mm³ ,  hold gemcitabine.

• Monitor serum creatinine, potassium, calcium, and magnesium in patients taking cisplatin with gemcitabine.
• Monitor hepatic and renal function before and periodically during therapy. May transiently ↑ in AST, ALT, alkaline phosphatase, and bilirubin concentrations.  If severe hepatic toxicity or hemolytic-uremic syndrome occurs,  discontinue gemcitabine.
• May cause ↑ BUN and serum creatinine, proteinuria, and hematuria.

Implementation

• High Alert: 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 2nd practitioner independently double-check original order, calculations, and infusion pump settings.

Patient/Family Teaching

• Explain purpose and side effects of gemcitabine to patient. Do not stop receiving drug without consulting health care provider. If an appointment is missed, contact health care provider as soon as possible to reschedule. Advise patient to read  Medication Guide  before starting and periodically during therapy in case of changes.
• Emphasize the need for periodic lab tests to monitor for side effects.
• Instruct patient to notify health care provider 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 provider if flulike 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, ↑ bruising or bleeding), or hepatotoxicity (jaundice, pain/tenderness in right upper abdominal quadrant) occur.
• Instruct patient to notify health care provider if any rash (particularly with fever, flu-like symptoms, swollen lymph nodes) develops within 1–2 wk of starting therapy.
• Discuss with patient the possibility of hair loss. Explore methods of coping.
• Instruct patient not to receive any vaccinations without advice of health care provider.
• Rep:   May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after final dose and to avoid breastfeeding during therapy and for ≥1 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. May cause male infertility.

Evaluation/Desired Outcomes

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