Fluorouracil Topical and Celecoxib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Celecoxib
Fluorouracil Topical
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 celecoxib exposure and an increased risk of celecoxib-related adverse effects
Interaction Deep Dive
Coadministration of capecitabine or doxifluridine or fluorouracil (prodrugs of capecitabine) or tegafur (prodrug of fluorouracil) with celecoxib (a CYP2C9 substrate) may increase celecoxib exposure which may increase the risk of adverse reactions related to celecoxib. Closely monitor for adverse reactions of celecoxib where minimal concentration changes may lead to serious adverse reactions when used concomitantly with capecitabine or doxifluridine or fluorouracil (prodrugs of capecitabine) or tegafur (prodrug of fluorouracil)1. Concomitant use of capecitabine and celecoxib has significantly increased the exposure of celecoxib compared with celecoxib alone (Cmax increased by 24% to 39%; AUC(0 to 8 hours) increased by 28% to 41%) in a pharmacokinetic study in 16 patients with advanced solid malignancies that was terminated after an interim analysis demonstrated a drug interaction. Reported adverse events were attributed to capecitabine 2.
Why it happens (mechanism)
Inhibition of CYP2C9-mediated metabolism of celecoxib
Literature reports
2 reports — tap to read
a) Concomitant administration of multiple doses of capecitabine (1000 mg/m(2) twice daily for 14 days) increased celecoxib AUC by 28%, Cmax by 24%, and Ctrough by 30% 1.
b) Concomitant use of capecitabine and celecoxib has significantly increased the exposure of celecoxib compared with celecoxib alone in a pharmacokinetic study in 16 patients with advanced solid malignancies that was terminated after an interim analysis demonstrated a drug interaction. Celecoxib Cmax increased from 1109 to 1377 nanograms (ng)/mL at steady-state after 7 days of coadministration (geometric mean ratio (GMR), 1.24 [90% CI, 1.04 to 1.49) and AUC (0 to 8 hours) increased from 5199 to 6656 ng x hr/mL (GMR, 1.28 [90% CI, 1.11 to 1.47]). After continued concomitant use followed by a 7-day washout period of capecitabine on day 21, there was an even greater increase in celecoxib Cmax (GMR, 1.39 [90% CI, 1.16 to 1.66) as well as the AUC(0 to 8 hours) (GMR, 1.41 [90% CI, 1.19 to 1.68]). Reported adverse events were attributed to capecitabine. Patient received celecoxib 200 mg orally twice daily with or without capecitabine 1000 mg/m(2) orally twice daily for 14 days on/7 days off for 21-day cycles 2.
Common questions
Can I take Fluorouracil Topical and Celecoxib together?
Increased celecoxib exposure and an increased risk of celecoxib-related adverse effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluorouracil Topical and Celecoxib 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Fluorouracil Topical or Celecoxib 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 (2)
- Product Information: XELODA(R) oral tablets, capecitabine oral tablets. Genentech USA Inc (per FDA), South San Francisco, CA, 2022. DailyMed
- Ramirez J, House LK, Karrison TG, et al: Prolonged pharmacokinetic interaction between capecitabine and a CYP2C9 substrate, celecoxib. J Clin Pharmacol 2019; 59(12):1632-1640. DOI
Keep reading about Celecoxib
Keep reading about Fluorouracil Topical
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