Febuxostat and Theophylline: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Febuxostat
Theophylline
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 exposure to 1-methylxanthine, one of the major metabolites of theophylline
Interaction Deep Dive
A drug interaction study in health patients demonstrated that concomitant administration of febuxostat and theophylline resulted in an approximate 400-fold increase in the amount of 1 methylxanthine excreted in urine as a result of xanthine oxidase inhibition by febuxostat. 1-methylxanthine is one of the major theophylline metabolites and the safety of its long-term exposure has not been evaluated. Although no dose adjustment is warranted for theophylline when used concomitantly with febuxostat, caution should be used since the safety of long-term exposure to 1-methylxanthine has not been determined1.
Why it happens (mechanism)
Inhibition of xanthine oxidase-mediated theophylline metabolism by febuxostat
Literature reports
2 reports — tap to read
a) During in vivo drug interaction studies, administration of 80 mg febuxostat once daily with theophylline resulted in a 6% increase in Cmax and a 6.5% increase in AUC of theophylline. These increases were not considered to be clinically significant. However, there was also an approximate 400-fold increase in the amount of 1-methylxanthine, a major metabolite of theophylline, excreted in the urine. The increase in 1-methylxanthine was a result of the inhibition of xanthine oxidase metabolism of theophylline by febuxostat. The effects of long-term exposure to 1-methylxanthine is unknown 1.
b) A drug interaction study evaluating the effect of febuxostat (xanthine oxidase inhibitor) upon the pharmacokinetics of theophylline (xanthine oxidase substrate) in healthy patients showed that coadministration of febuxostat with theophylline resulted in an approximately 400-fold increase in the amount of 1-methylxanthine, one of the major metabolites of theophylline, excreted in the urine. Since the long-term safety of exposure to 1-methylxanthine in humans is unknown, use with caution when coadministering febuxostat with theophylline 1.
Common questions
Can I take Febuxostat and Theophylline together?
Increased exposure to 1-methylxanthine, one of the major metabolites of theophylline Always confirm with your pharmacist or prescriber before making any change.
How serious is the Febuxostat and Theophylline 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 Febuxostat or Theophylline 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: ULORIC oral tablets, febuxostat oral tablets. Takeda Pharmaceuticals America Inc (per FDA), Deerfield, IL, 2023. DailyMed
Keep reading about Febuxostat
Keep reading about Theophylline
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