Febuxostat
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Dosing and administration[2]
Oral once daily, with or without food (may be given with antacids). Xanthine oxidase inhibitor, generally reserved for patients in whom allopurinol is ineffective or not tolerated. Co-prescribe flare prophylaxis on initiation.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Gout (urate lowering) | 40 mg once daily to start; if serum urate remains at or above 360 micromol/L (6 mg/dL) after about 2 weeks, increase to 80 mg once daily (the maximum in Canada). The Canadian tablet strength is 80 mg. | Titrate to a serum urate target below 360 micromol/L (6 mg/dL). |
Onset. Serum urate falls within about 2 weeks; reassess and up-titrate as needed.
Renal adjustment. No dose adjustment for mild to moderate renal impairment (creatinine clearance 30 mL/min or above); limited data and caution in severe impairment.
Hepatic. Use with caution in hepatic impairment; monitor liver function (transaminase elevations reported).
Cardiovascular safety: in the CARES trial, febuxostat was associated with higher cardiovascular and all-cause mortality than allopurinol. It is generally reserved for patients who cannot use allopurinol, and cardiovascular status should be considered and monitored.
Monitoring
- Serum urate to guide titration.
- Liver function tests periodically.
- Assess and monitor cardiovascular risk (see the note below).
Contraindications
- Concurrent azathioprine or mercaptopurine.
- Known hypersensitivity to febuxostat.
Key interactions
- Azathioprine and mercaptopurine: contraindicated (xanthine oxidase inhibition markedly increases their toxicity, causing severe myelosuppression).
- Theophylline: use with caution.
Clinical notes
How it is used in gout
Xanthine oxidase inhibitor, an alternative to allopurinol within the treat-to-target strategy. Allopurinol remains the strongly preferred first-line agent; febuxostat is a reasonable alternative when allopurinol is not tolerated or not effective.[1]
Monitoring
Serial serum urate to titrate to target. For patients with a history of cardiovascular disease or a new cardiovascular event on febuxostat, switching to an alternative agent is conditionally recommended. Laboratory intervals per monograph.[1]
Common effects
Background clinical knowledge (not from the guideline): liver transaminase elevation, nausea, arthralgia, and rash; flare on initiation as with any ULT.
Important cautions
Background and monograph, not from the gout guideline beyond the switch recommendation: a cardiovascular safety signal (CARES trial; boxed warning regarding cardiovascular death) underlies the conditional recommendation to switch in patients with cardiovascular disease. Reconcile dosing, hepatic monitoring, and cardiovascular cautions with the product monograph.
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
- ULORIC (febuxostat tablets) Product Monograph. Takeda Canada, Health Canada authorized product monograph. https://pdf.hres.ca/dpd_pm/00043863.PDF