Febuxostat and Tramadol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tramadol
Febuxostat
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 traMADol exposure and reduced exposure of the active metabolite
Interaction Deep Dive
Concomitant use of traMADol and a CYP2D6 inhibitor may increase exposure of traMADol, and reduce exposure of M1, the active metabolite of traMADol and reduce in M1 exposure, particularly when an inhibitor is added after a stable dose of traMADol is achieved. Reduced M1 exposure could result in reduced therapeutic effects, and may result in signs and symptoms of opioid withdrawal and reduced efficacy while an increase in traMADol exposure can increase the risk of seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the traMADol exposure will decrease and the M1 plasma concentration will increase. This could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, such as potentially fatal respiratory depression. If use of a CYP2D6 inhibitor is necessary in a patient receiving traMADol, closely monitor for seizures, serotonin syndrome, or opioid withdrawal. When discontinuing a CYP2D6 inhibitor in a patient receiving traMADol, consider a traMADol dose reduction and monitor for signs of respiratory depression or sedation1. Coadministration of traMADol and a strong CYP2D6 inhibitor resulted in significantly higher breakthrough opioid consumption compared with traMADol administration without a CYP2D6 inhibitor 2.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of traMADol
Literature reports
1 report — tap to read
a) In a retrospective study, the coadministration of traMADol and a strong CYP2D6 inhibitor (eg, FLUoxetine, PARoxetine, buPROPion) resulted in a significant increase in morphine milligram equivalents (MME) required for breakthrough pain compared with traMADol administration without a strong CYP2D6 inhibitor (N=152). The mean breakthrough MME per day was 18.3 mg for the traMADol/CYP2D6 inhibitor group and 5.7 mg for the control group; mean total breakthrough MME was also higher in the traMADol/CYP2D6 inhibitor group (42.4 mg vs 10.2 mg) 2.
Common questions
Can I take Febuxostat and Tramadol together?
Increased traMADol exposure and reduced exposure of the active metabolite Always confirm with your pharmacist or prescriber before making any change.
How serious is the Febuxostat and Tramadol 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 "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Febuxostat or Tramadol 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: Tramadol hydrochloride oral tablets, tramadol hydrochloride oral tablets. Strides Pharma, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
- Frost DA, Soric MM, Kaiser R, et al: Efficacy of tramadol for pain management in patients receiving strong cytochrome P450 2D6 inhibitors. Pharmacotherapy 2019; 39(6):724-729. PubMed
Keep reading about Tramadol
Keep reading about Febuxostat
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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