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, DPYD gene testing, 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 a risk that exists before treatment starts.

DPD (dihydropyrimidine dehydrogenase) is an enzyme that breaks down fluorouracil. The DPYD gene holds the instructions for making it. Some people have DPYD variants that lower or remove DPD activity. That is called DPD deficiency. The gene test and the enzyme problem are not the same thing. The test looks at the gene. The deficiency is the lack of working enzyme.

FDA now recommends testing for DPYD variants before fluorouracil or capecitabine. The exception is when treatment is needed right away.

FDA says people with complete DPD deficiency are at risk of serious or fatal reactions. Examples are mouth sores, diarrhea, low white blood cells and nerve problems. These can start early. People with partial deficiency can have serious or fatal reactions too. The label says to avoid fluorouracil in people known to have certain complete-deficiency variants. For partial deficiency, the label says the dose should be individualized. Your oncology team makes those choices, not you.

A test has limits. FDA says serious reactions can still happen even if no DPYD variant is found. FDA also says no FDA-authorized DPYD test is currently available, and the tests in use differ in which variants they check.

So ask your oncology team two things. Was DPYD testing done, or is it planned? What did it show, and what can it not show?

Call your oncology team right away if you have severe diarrhea, mouth sores or mouth pain, a fever or signs of infection, or other severe symptoms. This matters most in the first days of treatment. Do not wait for the next visit. Do not stop or change treatment on your own. The label tells the team to hold or permanently stop the drug if early or unusually severe toxicity appears. They can only do that if they know.

• 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?
• Was DPYD testing done or planned, and what did the result show?
• 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