• 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 Grade 3 or 4 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) occurs; hold fluorouracil until resolution to ≤Grade 1. 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 SUBQ 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, swelling, desquamation) throughout therapy. Occurs more frequently with continuous infusion. Usually occurs after 8–9 wk of therapy, but may occur earlier. Hold fluorouracil for Grades 2 or 3 and resume at lower dose when resolved or Grade 1.
  • Monitor intake and output, appetite, and nutritional intake. GI effects usually occur on 4th day of therapy. Adjusting diet as tolerated and administering antidiarrheal agents may help maintain fluid and electrolyte balance and nutritional status. May cause severe diarrhea. Withhold therapy if Grade 3 or 4 diarrhea occurs and until resolved or decreased to Grade 1; then resume at reduced dose.
  • Monitor for cerebellar dysfunction (ataxia, confusion, disorientation, visual disturbances). This may persist after discontinuation of therapy.
  • Monitor for angina, myocardial infarction/ischemia, arrhythmia, and HF in patients with no history of coronary artery disease or cardiac dysfunction. Discontinue therapy if symptoms occur.
  • Monitor for signs and symptoms of hyperammonemic encephalopathy (altered mental status, confusion, disorientation, coma, ataxia) with ↑ serum ammonia level within 72 hr of start of infusion. Discontinue fluorouracil and initiate ammonia-lowering therapy.
  • Assess for mucositis, stomatitis, and esophagopharyngitis during therapy. May lead to mucosal sloughing or ulceration. Occurs more frequently with IV bolus doses. If Grade 3 or 4 mucositis occurs, withhold dose and resume at reduced dose when resolved or reduced to Grade 1.
• Topical Inspect involved skin before and throughout therapy.

Lab Test Considerations:

• May cause ↓ in plasma albumin.
  • Consider testing for genetic variants of the DPYD gene prior to initiating fluorouracil to reduce the risk of serious adverse reactions. Patients with certain variants in this gene may have dihydropyrimidine dehydrogenase deficiency, which can result in serious adverse reactions including mucositis, diarrhea, neutropenia, and neurotoxicity.
  • Monitor hepatic (AST, ALT, LDH, and serum bilirubin), renal, and hematologic (hematocrit, hemoglobin, leukocyte, platelet count) functions before each treatment 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. Hold doses if Grade 4 myelosuppression occurs. Resume at ↓ dose when resolved or improved to Grade 1.
  • May cause ↑ in urine excretion of 5-hydroxyindoleacetic acid.