5-FU (Fluorouracil): What It Is and What to Expect

This page is for people having fluorouracil (5-FU) chemotherapy, and their families. It covers how the drug works, its approved uses and doses, the DPD enzyme test, the label's warnings, and questions to ask.

Fluorouracil is an antimetabolite. NCI describes that as a drug that mimics a natural chemical and prevents its use in cells.

The mechanism has two halves. First, it blocks the making of a key part of DNA. DNA can then no longer copy itself. Second, it gets built into RNA and DNA directly, and disrupts how the cell works. Cells that divide fastest feel it first. That is why the mouth, the gut lining and the bone marrow are where trouble shows up.

5-FU is shorthand for the chemical name, not a brand. NCI's page for the injection lists Carac as a US brand name, and notes that a topical form of fluorouracil exists separately.

The FDA label for fluorouracil injection names four indications:

• Adenocarcinoma of the colon and rectum.
• Adenocarcinoma of the breast.
• Gastric adenocarcinoma.
• Pancreatic adenocarcinoma.

NCI's drug page lists the same four. Anything beyond that list is off-label use. Off-label use is legal and often reasonable. It is simply a different conversation.

Chemotherapy doses are often treated as unknowable. For this drug they are published. Knowing which schedule is in use explains a lot about how a week will feel.

• Colon and rectum, infusional. An injection on day 1, then a continuous infusion over 46 hours, every two weeks. Leucovorin goes with it. So often does oxaliplatin or irinotecan.
• Colon and rectum, bolus. Injections on days 1, 8, 15, 22, 29 and 36, in 8-week cycles, with leucovorin.
• Breast. Given on days 1 and 8. Every 28 days, for 6 cycles. It sits inside a cyclophosphamide-based regimen.
• Stomach. A continuous infusion over 24 hours, within a platinum-containing regimen.
• Pancreas. An injection on day 1, then a continuous infusion over 46 hours, every two weeks.

The label also says the dose is individualized. Tumor type, the regimen, disease state, response and risk factors all feed into it. So a number that differs from the ones above is not automatically an error.

The long infusions run through a small portable pump. That is why people go home still attached, and come back to be disconnected.

This is the risk that exists before treatment starts.

Dihydropyrimidine dehydrogenase (DPD) is the enzyme that clears fluorouracil from the body. Some people carry gene variants that leave them with almost none of it.

The label is specific. Those patients face a raised risk of acute early-onset toxicity. They also face severe, life-threatening or fatal reactions. The examples given are mucositis, diarrhea, neutropenia and nerve toxicity. Partial DPD activity raises risk too. No dose has been proven safe in a person with absent DPD activity.

The label's instruction to the treating team is blunt: withhold or permanently stop the drug when there is evidence of acute early-onset toxicity, or of unusually severe toxicity. Your part is the reporting. Call your care team right away if severe mouth pain, diarrhea or fever starts. The sooner the team knows, the sooner that rule can protect you.

• Cardiotoxicity (heart damage). Angina, myocardial infarction or ischemia, arrhythmia and heart failure. The drug is withheld for cardiac toxicity.
• Hyperammonemic encephalopathy (brain effects from high ammonia). Altered mental state, confusion, disorientation, coma or unsteadiness with a raised ammonia level, within 72 hours of starting.
• Neurologic toxicity (nerve and brain effects). Acute cerebellar syndrome, confusion, disorientation, unsteadiness or visual disturbance.
• Diarrhea. Severe cases mean withholding the drug until it resolves.
• Hand-foot syndrome. Redness, soreness and peeling of palms and soles. Severe cases mean stopping until it settles, then resuming at a lower dose.
• Myelosuppression (low blood counts). The label calls it severe and potentially fatal.
• Mucositis (sore, inflamed lining of the mouth and gut). Same rule: stop, let it resolve, resume lower.
• Warfarin interaction. Giving the two together can raise clotting test values. INR and prothrombin time are watched closely.
• Embryo-fetal toxicity (harm to an unborn baby). The drug can harm a fetus.

Reports made after the drug went on sale add more:

• photosensitivity (skin that burns easily in sunlight)
• nail changes, including loss of nails
• vein pigmentation (darkening along the veins)
• blocked tear ducts
• nosebleeds

These come from voluntary reports, so their true frequency is not known.

• Which of the label's warnings apply to my other conditions?
• Has DPD deficiency been considered, and is testing available here?
• Is leucovorin part of this regimen, and what is it doing?
• Which of my other medicines interact with fluorouracil?
• What mouth care is recommended before mucositis starts?
• What should be done about palms and soles before they get sore?
• What happens if a dose is missed, or a pump finishes late?
• Which number is answered outside office hours?

Ask about mouth care and hand and foot care before the first cycle, not after problems start.

This page summarizes. It does not replace the prescribing information. That document is written and kept current by the reviewers who approved the drug.

The FDA-approved label is on DailyMed, the National Library of Medicine's official label database. Three sections matter most: the Warnings and Precautions, the Adverse Reactions, and the patient leaflet.

Trouble breathing, chest pain, confusion or heavy bleeding are emergencies with any cancer drug: call 911 or go to an emergency department, not to a website. A fever of 100.4°F (38°C) or higher during chemotherapy is also an emergency. CDC calls it a medical emergency and says to call your doctor right away. Go to an emergency department if needed, and tell staff you are having chemotherapy. Do not drive yourself.

For how this drug fits into a wider plan, see chemotherapy and understanding your treatment plan.

• NCI — Fluorouracil Injection
• openFDA drug label API — fluorouracil injection (intravenous)
• CDC — Watch out for fever during cancer treatment
• DailyMed — fluorouracil label search