Fluorouracil and Folic Acid: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Folic Acid
Fluorouracil
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased capecitabine or doxifluridine or fluorouracil (prodrugs of capecitabine) or tegafur (prodrug of fluorouracil) exposure and an increased risk of capecitabine or doxifluridine or fluorouracil or tegafur-related toxicity
Interaction Deep Dive
Coadministration of capecitabine or doxifluridine or fluorouracil (prodrugs of capecitabine) or tegafur (prodrug of fluorouracil) with folic acid may increase the exposure of capecitabine or doxifluridine or fluorouracil or tegafur and may enhance its toxicity. Instruct patients not to take folate analog products unless directed to do so1.
Why it happens (mechanism)
Unknown
Common questions
Can I take Fluorouracil and Folic Acid together?
Increased capecitabine or doxifluridine or fluorouracil (prodrugs of capecitabine) or tegafur (prodrug of fluorouracil) exposure and an increased risk of capecitabine or doxifluridine or fluorouracil or tegafur-related toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluorouracil and Folic Acid interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Fluorouracil or Folic Acid need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: XELODA(R) oral tablets, capecitabine oral tablets. Genentech USA Inc (per FDA), South San Francisco, CA, 2022. DailyMed
Keep reading about Folic Acid
Keep reading about Fluorouracil
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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