Febuxostat

Selective xanthine oxidase inhibitor

ATC code: M04AA03

Brand names: Uloric, Goturic

Updated 27 May 2026 · Methodology

Indications

Gout prevention (urate-lowering therapy)

Second line

Second-line agent in gout after allopurinol per 2016 and 2020. Used with allopurinol intolerance, inadequate response on maximum tolerated allopurinol dose, or in HLA-B*5801 positive status (raised risk of allopurinol hypersensitivity). Standard dose 80 mg once daily; up-titrate to 120 mg if target urate is not reached. Goal: serum urate under 6 mg/dL (under 5 mg/dL in severe tophaceous gout). The CARES trial (2018) showed higher cardiovascular mortality versus allopurinol – indications have since been narrowed.

Sources

ICD-10: M10.9 · ICD-11: FA25

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Asymptomatic hyperuricemia

Not recommended

Febuxostat is actively prescribed to patients with asymptomatic hyperuricemia without gout or nephrolithiasis for anti-aging uric acid reduction. 2020 and 2023 recommend against treating asymptomatic hyperuricemia in patients without gout flares or urate nephropathy. CARES 2018 (White) in gout patients with cardiovascular disease showed increased cardiovascular mortality versus allopurinol, prompting an boxed warning 2019 on increased mortality. Use in asymptomatic patients is unjustified.

Sources

ICD-10: E79.0 · ICD-11: 5C55

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A selective non-purine xanthine oxidase inhibitor – the enzyme converting hypoxanthine to xanthine and xanthine to uric acid. Unlike allopurinol, it inhibits both oxidized and reduced enzyme forms and produces stronger urate lowering at equipotent doses. No dose adjustment is needed in mild-to-moderate renal impairment (eGFR over 30). Half-life 5–8 hours; once-daily dosing.

Safety

Contraindications

Febuxostat hypersensitivity
Concurrent azathioprine, mercaptopurine (risk of severe myelosuppression)
Severe hepatic impairment

Serious adverse effects

Higher cardiovascular mortality in CVD patients (CARES trial)
Severe cutaneous reactions (Stevens–Johnson syndrome, DRESS)
Hepatotoxicity
Anaphylaxis
Acute kidney injury

Common adverse effects

Gout flare in the first months
Elevated liver enzymes
Nausea, diarrhea
Headache
Rash

Pregnancy: can you take Febuxostat?

Limited data. Urate-lowering therapy is generally not indicated in pregnancy – acute flares are treated with glucocorticoids or NSAIDs after T1. Febuxostat is not used.

Breastfeeding: can you take Febuxostat?

No data on milk excretion. Not used during lactation.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily, with or without food. Start therapy between flares – a rapid urate drop in the first weeks can trigger a gout flare. For flare prophylaxis in the first 6 months, give concurrent colchicine 0.5 mg 1–2 times daily or an NSAID. Before starting febuxostat in patients with cardiovascular disease, assess cardiovascular risk – per the 2019 warning, allopurinol is preferred in patients with CVD.

Drug–drug interactions

1 pair found. Sorted from critical to minor.

CriticalAzathioprineImmunosuppressants, thiopurines

Mechanism

Febuxostat inhibits xanthine oxidase, the enzyme that converts 6-mercaptopurine, the active metabolite of azathioprine, into an inactive form. In an interaction study febuxostat reduced 6-mercaptopurine clearance by about 83% after a single dose of azathioprine. The lists the combination as a contraindication in section 4 of the febuxostat label. The EU SmPC does not recommend it and, if it cannot be avoided, requires cutting the azathioprine dose to 20% or less of the previous dose.

Symptoms

Same as with allopurinol: pancytopenia with fever, infections and bleeding within the first weeks of therapy.

Management

Combination contraindicated. To treat hyperuricaemia in patients on azathioprine, use other classes: probenecid if renal function is preserved or pegloticase for severe gout.

Sources

Pair details →Azathioprine →

Label mentions16 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

CriticalAzathioprine
«CONTRAINDICATIONS: Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine [see Drug Interactions (7) ] .»
FDA, section 4 · Open on DailyMed
MajorAzathioprine
«Mercaptopurina/azatioprina: Dado el mecanismo de acción de febuxostat sobre la inhibición de la XO, no se recomienda su uso concomitante. La inhibición de la XO por febuxostat puede ocasionar un…»
AEMPS, section 4.5 · Open on CIMA
ModerateTheophylline
«Xanthine Oxidase Substrate Drugs: Febuxostat tablet is an XO inhibitor. Based on a drug interaction study in healthy patients, febuxostat altered the metabolism of theophylline (a substrate of XO) in…»
FDA, section 7 · Open on DailyMed
AINEclass named in the label
«Naproxeno y otros inhibidores de la glucuronidación: Los medicamentos que inhiben la glucuronidación, como los AINE o el probenecid, podrían teóricamente afectar la eliminación del febuxostat. En…»
AEMPS, section 4.5 · Open on CIMA
antiácidosclass named in the label
«Antiácidos: Se ha demostrado que la ingestión concomitante de un antiácido que contenga hidróxidos de magnesio y aluminio retrasa la absorción de febuxostat (alrededor de 1 hora) y provoca una…»
AEMPS, section 4.5 · Open on CIMA
antineoplásicosclass named in the label
«No se han realizado estudios de interacciones farmacológicas de febuxostat con otros quimioterápicos citotóxicos. Por tanto, no hay datos disponibles sobre la seguridad de febuxostat durante el…»
AEMPS, section 4.5 · Open on CIMA
antineoplasticsclass named in the label
«Cytotoxic Chemotherapy Drugs: Drug interaction studies of febuxostat tablets with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of febuxostat tablets…»
FDA, section 7 · Open on DailyMed
Colchicine
«In Vivo Drug Interaction Studies: Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin…»
FDA, section 7 · Open on DailyMed
Hydrochlorothiazide
«In Vivo Drug Interaction Studies: Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin…»
FDA, section 7 · Open on DailyMed
Naproxen
«In Vivo Drug Interaction Studies: Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin…»
FDA, section 7 · Open on DailyMed
Theophylline
«Teofilina: Se ha realizado un estudio de interacción con febuxostat en sujetos sanos para evaluar si la inhibición de la XO puede provocar un incremento de la concentración de teofilina circulante…»
AEMPS, section 4.5 · Open on CIMA
thiazide diureticsclass named in the label
«In Vivo Drug Interaction Studies: Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin…»
FDA, section 7 · Open on DailyMed
Warfarin
«In Vivo Drug Interaction Studies: Based on drug interaction studies in healthy patients, febuxostat tablets do not have clinically significant interactions with colchicine, naproxen, indomethacin…»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

MajorAzathioprine
«Según los datos preclínicos, otros inhibidores de la xantina oxidasa (p. ej., febuxostat) pueden prolongar la actividad de la azatioprina, lo que podría derivar en una mayor supresión de la médula…»
AEMPS, section 4.5 · Open on CIMA
MajorAzathioprine
«DRUG INTERACTIONS: Use with xanthine oxidase (XO) inhibitors: One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving…»
FDA, section 7 · Open on DailyMed
Theophylline
«alopurinol, febuxostat,»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Febuxostat used for?

Febuxostat is evaluated for the following indications with varying evidence strength: Gout prevention (urate-lowering therapy) (evidence tier A), Asymptomatic hyperuricemia (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Febuxostat?

Common side effects of Febuxostat (≥ 1 in 100): Gout flare in the first months, Elevated liver enzymes, Nausea, diarrhea, Headache, Rash. See the Safety section for uncommon and serious reactions.

Is Febuxostat safe during pregnancy?

Limited data. Urate-lowering therapy is generally not indicated in pregnancy – acute flares are treated with glucocorticoids or NSAIDs after T1. Febuxostat is not used.

Is Febuxostat compatible with breastfeeding?

No data on milk excretion. Not used during lactation.

Who should not take Febuxostat?

Febuxostat is contraindicated in: Febuxostat hypersensitivity; Concurrent azathioprine, mercaptopurine (risk of severe myelosuppression); Severe hepatic impairment. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 06/30/2025
EMALabel dated 06/15/2017
FDA / DailyMedLabel dated 03/10/2026

Other drugs in this group

Allopurinol, Colchicine