High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.
Pronunciation: Online audio
- IV: Used alone and in combination with other modalities (surgery, radiation therapy, other antineoplastics) in the treatment of:
- Colon cancer,
- Breast cancer,
- Rectal cancer,
- Gastric cancer,
- Pancreatic carcinoma.
- Topical: Management of multiple actinic (solar) keratoses and superficial basal cell carcinomas.
Inhibits DNA and RNA synthesis by preventing thymidine production (cell-cycle S-phase–specific).
Death of rapidly replicating cells, particularly malignant ones.
Absorption: Minimal absorption (5–10%) after topical application.
Distribution: Widely distributed; concentrates and persists in tumors.
Metabolism and Excretion: Metabolized by dihydropyrimidine dehydrogenase to a less toxic compound; inactive metabolites are excreted primarily in urine.
Half-life: 20 hr.
TIME/ACTION PROFILE (IV = effects on blood counts, Top = dermatologic effects)
|IV||1–9 days||9–21 days (nadir)||30 days|
|Top||2–3 days||2–6 wk||1–2 mo|
- Dihydropyrimidine dehydrogenase deficiency (patients at ↑ risk of 5–FU toxicity)
- OB: Lactation: Pregnancy or lactation.
Use Cautiously in:
- Depressed bone marrow reserve
- Other chronic debilitating illnesses
- Obese patients, patients with edema or ascites (dose should be based on ideal body weight).
Adverse Reactions/Side Effects
More likely to occur with systemic use than with topical use
CNS: acute cerebellar dysfunction
GI: diarrhea, nausea, stomatitis, vomiting
Derm: alopecia, maculopapular rash, local inflammatory reactions (topical only), melanosis of nails, nail loss, palmar-plantar erythrodysesthesia, phototoxicity
Hemat: anemia, leukopenia, thrombocytopenia
* CAPITALS indicate life-threatening.
Italics indicate most frequent.
- Combination chemotherapy with irinotecan may produce unacceptable toxicity (dehydration, neutropenia, sepsis).
- May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
Doses may vary greatly, depending on tumor, patient condition, and protocol used
Advanced Colorectal Cancer
IV: (Adults) 370 mg/m2 preceded by leucovorin or 425 mg/m2 preceded by leucovorin daily for 5 days. May be repeated q 4–5 wk.
IV: (Adults) Initial dose–12 mg/kg/day for 4 days, then 1 day of rest, then 6 mg/kg every other day for 4–5 doses or 7–12 mg/kg/day for 4 days followed by 3-day rest, then 7–10 mg/kg q 3–4 days for 3 doses. Maintenance–7–12 mg/kg q 7–10 days or 300–500 mg/m2/day for 4–5 days, repeated monthly (no single daily dose should exceed 800 mg). Poor-Risk Patients: 3–6 mg/kg/day on days 1–3, 3 mg/kg/day on days 5, 7, 9 (not to exceed 400 mg/dose). Doses of 370–425 mg/m2/day for 5 days have been used in combination with leucovorin.
Actinic (Solar) Keratoses
Topical: (Adults) Carac–Apply 0.5% cream to lesions once daily for up to 4 wk; Efudex–Apply 2% or 5% solution or cream to lesions twice daily for 2–4 wk; Fluoroplex–Apply 1% cream to lesions twice daily for 2–6 wk.
Superficial Basal Cell Carcinomas
Topical: (Adults) Efudex–Apply 5% solution or cream to lesions twice daily for 3–6 wk (up to 12 wk).
Availability (generic available)
Injection: 50 mg/mL
Cream: 0.5%, 1%, 5%
Solution: 2%, 5%
- Monitor vital signs before and frequently during therapy.
- Assess mucous membranes, number and consistency of stools, and frequency of vomiting. Assess for signs of infection (fever, chills, sore throat, cough, hoarseness, pain in lower back or side, difficult or painful urination). Assess for bleeding (bleeding gums; bruising; petechiae; and guaiac test stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min. Notify health care professional if symptoms of toxicity (stomatitis or esophagopharyngitis, uncontrollable vomiting, diarrhea, GI bleeding, myocardial ischemia, leukocyte count <3500/mm3, platelet count <100,000/mm3, or hemorrhage from any site) occur; drug will need to be discontinued. May be reinitiated at a lower dose when side effects have subsided.
- Assess IV site frequently for inflammation or infiltration. Patient should notify nurse if pain or irritation at injection site occurs. May cause thrombophlebitis. If extravasation occurs, infusion must be stopped and restarted in another vein to avoid damage to subcut tissue. Report immediately. Standard treatment includes application of ice compresses.
- Assess skin for palmar-plantar erythrodysesthesia (tingling of hands and feet followed by pain, erythema, and swelling) throughout therapy.
- Monitor intake and output, appetite, and nutritional intake. GI effects usually occur on 4th day of therapy. Adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
- Monitor patient for cerebellar dysfunction (weakness, ataxia, dizziness). This may persist after discontinuation of therapy.
- Topical: Inspect involved skin before and throughout therapy.
Lab Test Considerations:
May cause ↓ in plasma albumin.
- Monitor hepatic (AST, ALT, LDH, and serum bilirubin), renal, and hematologic (hematocrit, hemoglobin, leukocyte, platelet count) functions before and periodically during therapy. Monitor CBC daily during IV therapy. Report WBC of <3500/mm3 or platelets <100,000/mm3 immediately; they are criteria for discontinuation. Nadir of leukopenia usually occurs in 9–14 days, with recovery by day 30. May also cause thrombocytopenia.
- May cause ↑ in urine excretion of 5-hydroxyindoleacetic acid (5-HIAA).
- 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 second practitioner independently double check original order, calculations and infusion pump settings. The number 5 in 5-fluorouracil is part of the drug name and does not refer to the dose.
- Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Topical: Consult health care professional before administering topical preparations to determine which skin preparation regimen should be followed. Tight occlusive dressings are not advised because of irritation to surrounding healthy tissue. A loose gauze dressing for cosmetic purposes is usually preferred. Wear gloves when applying medication. Do not use metallic applicator.
- Direct IV: Diluent: May be administered undiluted. Concentration 50 mg/mL.
- Rate: Rapid IV push administration (over 1–2 min) is most effective, but there is a more rapid onset of toxicity.
- Intermittent Infusion: Diluent: May be diluted with D5W or 0.9% NaCl.
- Use plastic IV tubing and IV bags to maintain greater stability of medication. Solution is stable for 24 hr at room temperature; do not refrigerate. Solution is colorless to faint yellow. Discard highly discolored or cloudy solution. If crystals form, dissolve by warming solution to 140°F, shaking vigorously, and cooling to body temperatureConcentration Up to 50 mg/mL.
- Rate: Onset of toxicity is greatly delayed by administering an infusion over 2–8 hr.
- Y-Site Compatibility
- amphotericin B lipid complex
- amphotericin B liposome
- calcium gluconate
- doxorubicin liposome
- etoposide phosphate
- magnesium sulfate
- potassium acetate
- potassium chloride
- potassium phosphates
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- vitamin B complex with C
- zolendronic acid
- Y-Site Incompatibility
- amphotericin B cholesteryl
- amphotericin B colloidal
- calcium chloride
- Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; yellowing of skin or eyes; abdominal pain; joint or flank pain; swelling of feet or legs; 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. Patients should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
- Advise patient to rinse mouth with clear water after eating and drinking and to avoid flossing to minimize stomatitis. Viscous lidocaine may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
- Discuss with patient the possibility of hair loss. Explore methods of coping.
- Review with patient the need for contraception during therapy.
- Caution patient to use sunscreen and protective clothing to prevent phototoxicity reactions.
- Instruct patient not to receive any vaccinations without advice of health care professional.
- Emphasize the importance of routine follow-up lab tests to monitor progress and to check for side effects.
- Topical: Instruct patient in correct application of solution or cream. Emphasize importance of avoiding the eyes; caution should also be used when applying medication near mouth and nose. If patient uses clean finger to self-administer, emphasize importance of washing hands thoroughly after application. Explain that erythema, scaling, and blistering with pruritus and burning sensation are expected. Advise patient to avoid sunlight or ultraviolet light (tanning booths) as much as possible; may increase side effects. Therapy is discontinued when erosion, ulceration, and necrosis occur in 2–6 wk (10–12 wk for basal cell carcinomas). Skin heals 4–8 wk later.
- Tumor regression.
- Removal of solar keratoses or superficial basal cell skin cancers.