A mainstay of many cancer treatments for decades, 5-fluorouracil (5-FU) injection package inserts were updated in March 2024 through the U.S. Food and Drug Administration’s (FDA’s) Project Renewal. The revisions add pharmacogenomics information and a safety warning about severe adverse reactions in patients with DPD deficiency. 

The DPYD gene provides instruction to create the DPD enzyme, which is a primary metabolizer of fluorouracil. Certain DPYD variants lead to DPD deficiency and puts patients at high risk for serious adverse reactions, which could be fatal. Patients with a known complete DPD deficiency should not receive 5-FU. The Clinical Pharmacogenetics Implementation Consortium provides recommendations for dose reductions based on differing DPYD genotypes.  

5-FU can be administered either via IV or topically. This drug reference sheet contains information about the IV version. 

This ONS resource was produced for educational purposes only. Refer to the full 5-FU package insert for all details. 

DRUG INFORMATION
ClassificationPyrimidine analog antimetabolite
Mechanism of ActionInhibits RNA formation and DNA synthesis by decreasing thymine, resulting in apoptosis
IndicationsTreatment of patients with breast, colon, rectal, gastric, or pancreatic cancer
ADMINISTRATION
Dosing, Frequency, and AdministrationDose varies based on indication, regimen, route, patient response to treatment, and patient risk factors
RouteIV bolus or infusion
Safe Handling5-FU is a hazardous drug. Follow safe handling precautions.
ADVERSE REACTIONS
Nausea, anorexia, vomiting, diarrhea, alopecia, ocular toxicities, darkening of veins, dry skin, neurotoxicity, hyperammonemia, encephalopathy, cardiotoxicity, risk of elevated international normalized ratio (INR) with warfarin, and embryo-fetal toxicity
WARNINGS
  • Increased risk for fatal adverse reactions in patients with DPD deficiency
  • Dose-limiting mucositis, cardiotoxicity, hyperammonemic encephalopathy, neurologic toxicity, diarrhea, embryo-fetal toxicity, myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome), and elevation of INR with warfarin
NURSING CONSIDERATIONS
Pretreatment
  • Do not administer within four weeks of potent DYPD inhibitors (e.g., brivudine, sorivudine).
  • Closely monitor prothrombin time and INR in patients on warfarin.
  • Administer leucovorin immediately prior to 5-FU, if indicated. 
  • Apply ice chips to the oral cavity 10–15 minutes before and after IV bolus, if needed, to reduce the risk or severity of oral mucositis.
Administration
  • Administer IV push or bolus over five minutes via the side arm (Y-site port) of fast-flowing compatible fluids.
  • Continuous IV infusion is administered via an elastomeric or electronic pump. 
  • 5-FU is incompatible with leucovorin. 
  • Protect from sunlight
Post-Treatment
  • Monitor for adverse reactions.
  • 5-FU IV push and continuous infusion have different toxicity profiles: IV push is more likely to cause mucositis and myelosuppression, whereas continuous infusion results in more diarrhea and palmar-plantar erythrodysesthesia. 
PATIENT EDUCATION
  • Patients of reproductive potential should use effective contraception during treatment and for three months after the final dose.
  • Use photosensitivity precautions year-round.
  • Watch for dehydration and electrolyte imbalances related to uncontrolled diarrhea, nausea, and vomiting.
  • Understand when and how to take home antidiarrheal and antinausea medications and when to call the provider or seek emergency care.
  • Watch for signs and symptoms of palmar-plantar erythrodysesthesia and use prevention methods.
  • Practice proper use of home infusion pumps, including starting, stopping, pausing, and turning off the pump and clamping the line. Keep written instructions about the pump, contact information for any pump issues, and a chemotherapy spill kit nearby.
RESOURCES
Patient Resources
  • Patient education sheets: 5-FU is a component of many cancer regimens. Search “fluorouracil” in the IV Cancer Treatment Education library to find patient education for specific regimens. 
  • Patient assistance programs: Find out which brand of 5-FU is used in your pharmacy’s formulary and check the manufacturer’s website. 
Healthcare Professional Resources
Other Resources