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

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.

Dipyrimidine dehydrogenase 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.

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 — the earlier severe mouth pain, diarrhea or fever reaches the team, the sooner that rule can protect you. And no dose has been proven safe in a person with absent DPD activity.

• Cardiotoxicity. Angina, myocardial infarction or ischemia, arrhythmia and heart failure. The drug is withheld for cardiac toxicity.
• Hyperammonemic encephalopathy. Altered mental state, confusion, disorientation, coma or unsteadiness with a raised ammonia level, within 72 hours of starting.
• Neurologic toxicity. 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. The label calls it severe and potentially fatal.
• Mucositis. 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. The drug can harm a fetus.

Postmarketing reports add more. Photosensitivity. Nail changes, including loss of nails. Vein pigmentation. 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?

Fluorouracil is old, cheap and still central to treatment for four common cancers. Most of what makes it manageable is anticipation rather than rescue. Mouth care starts before the sores. Hand and foot care starts before the peeling. The label's warnings are written in the order the reviewers thought mattered. Reading them in that order is a reasonable way to prepare for a first cycle.

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 during chemotherapy is also an emergency — call the care team's emergency number straight away or go to an emergency department.

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)
• DailyMed — fluorouracil label search