Mercaptopurine and Febuxostat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Febuxostat
Mercaptopurine
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 azaTHIOprine exposure and an increased risk of hepatotoxicity
Interaction Deep Dive
Concomitant use of azaTHIOprine and febuxostat is contraindicated due to a risk of azaTHIOprine toxicity. In a drug interaction study, Inhibition of xanthine oxidase by febuxostat caused increased exposure of 6-mercaptopurine, a metabolite of azaTHIOprine, which may lead to toxicity. During in vivo drug interaction studies, coadministration with febuxostat (40 mg or 120 mg QD) reduced the apparent clearance of mercaptopurine, a xanthine oxidase substrate, by 83.2% to 83.8% following a single oral dose of azaTHIOprine, a prodrug of 6-mercaptopurine. No significant differences were observed in the extent of inhibition of 6-mercaptopurine metabolism by febuxostat 40 mg and 120 mg2.Mercaptopurine is hepatotoxic. Hepatotoxicity may be increased when mercaptopurine is coadministered with other products that can cause hepatoxicity, such as febuxostat. There are reports of deaths attributed to hepatic necrosis associated with the administration of mercaptopurine. Hepatic injury can occur with any dosage but seems to occur with greater frequency when the recommended dosage is exceeded. Monitor serum transaminase levels, alkaline phosphatase, and bilirubin levels at weekly intervals when first beginning therapy and at monthly intervals thereafter. Monitor liver tests more frequently in patients who are receiving mercaptopurine with other hepatotoxic drugs or with known pre-existing liver disease. Withhold mercaptopurine at onset of hepatotoxicity 1.
Why it happens (mechanism)
Inhibition of xanthine oxidase-mediated azaTHIOprine metabolism; additive hepatotoxic effects
Literature reports
2 reports — tap to read
a) During in vivo drug interaction studies, coadministration with febuxostat (40 mg or 120 mg QD) reduced the apparent clearance of mercaptopurine, a xanthine oxidase substrate, by 83.2% to 83.8% following a single oral dose of azaTHIOprine, a prodrug of 6-mercaptopurine. No significant differences were observed in the extent of inhibition of 6-mercaptopurine metabolism by febuxostat 40 mg and 120 mg 2.
b) A drug interaction study of febuxostat and azaTHIOprine has been conducted. Inhibition of xanthine oxidase by febuxostat caused increased exposure of 6-mercaptopurine, a metabolite of azaTHIOprine, which may lead to toxicity. Drug interaction studies of febuxostat with other drugs that are metabolized by xanthine oxidase(e.g., mercaptopurine) have not been conducted 2.
Common questions
Can I take Mercaptopurine and Febuxostat together?
Increased azaTHIOprine exposure and an increased risk of hepatotoxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mercaptopurine and Febuxostat interaction?
It is rated contraindicated. These should generally not be used together.
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 Mercaptopurine or Febuxostat 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)
Keep reading about Febuxostat
Keep reading about Mercaptopurine
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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