Febuxostat is a newly introduced nonpurine xanthine oxidase inhibitor used for the treatment of gout. Chronic febuxostat therapy has been associated with minor serum aminotransferase elevations, but has yet to be linked to cases of clinically apparent acute liver injury.


Febuxostat (fe bux' oh stat) is a nonpurine inhibitor of xanthine oxidase that shares no structural homology to allopurinol or to hypoxanthine. Therapy with febuxostat leads to lowering of serum uric acid levels within a few weeks, and chronic therapy has been shown to decrease uric acid levels into target levels of <6 mg/dL and to decrease acute gouty attacks. Febuxostat was approved for use in Europe in 2008 and in the United States in 2009. Current indications include therapy and prevention of gout, uric acid nephropathy, and the hyperuricemia caused by malignancy and anticancer therapy. Febuxostat is not recommended as therapy of asymptomatic hyperuricemia. Febuxostat is available in tablets of 40 and 80 mg under the brand names of Uloric and Adenuric. The recommended initial dose for therapy of gout is 40 mg daily, which can be increased to 80 mg daily to achieve uric acid levels below 6 mg/dL. Common side effects include nausea, diarrhea, dizziness and precipitation of acute gout for which reason it is often given in combination with colchicine for the first few months of treatment.


Liver test abnormalities have been reported to occur in 2% to 13% (average ~3.5%) of patients receiving febuxostat, but the levels are generally mild-to-moderate and self-limited. The height, nature and timing of these abnormalities have not been described. However, liver test elevations were the major reason for febuxostat discontinuation for adverse events (~2%) in clinical trials, despite the fact that no cases of jaundice or acute hepatitis were reported. Since its approval and more wide-scale use, there have been several individual case reports of liver injury attributed to febuxostat. Most cases have been marked by serum aminotransferase elevations without jaundice arising within days of starting febuxostat, including enzyme elevations in the setting of DRESS syndrome. At least one instance of a mixed-cholestatic hepatitis without immunoallergic features, arising after several months of treatment has been described. The product label for febuxostat lists hepatic steatosis, hepatitis and hepatomegaly as potential side effects. Furthermore, several cases of acute liver failure during febuxostat therapy have been reported to pharmacovigilance databases. Another unrelated, nonpurine xanthine oxidase inhibitor (benzbromarone) was not approved for use in the United States because of its potential for hepatic toxicity.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism of febuxostat hepatotoxicity is believed to be due to its hepatic metabolism, the major pathway being glucuronidation with minor metabolism via the CYP 450 system.

Outcome and Management

The minor liver test abnormalities are reported to be self-limited, resolving with stopping the drug and, in many instances, resolving rapidly even with drug continuation. No instances of acute liver failure or chronic liver injury have been reported due to febuxostat, but the clinical experience with this agent is limited.

Drug Class: Antigout Agents



Febuxostat – Uloric®


Antigout Agents/Gout Suppressants


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 29 January 2018

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    (1086 subjects enrolled in extension study of febuxostat or allopurinol for 31-40 months; ALT elevations ultimately required withdrawal in 9 of 801 patients [1.1%] on febuxostat [80 mg/day], two episodes of jaundice, but both thought to be due to unrelated biliary disease--stone and bile duct cancer).
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  • Febuxostat: hepatic failure. Prescrire Int 2013; 22: 297. [PubMed: 24600733]
    (News report mentions that 13 reports of acute liver failure during febuxostat therapy have been reported to the European pharmacovigilance databse, 6 of which were fatal).
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    (Trial of two doses of febuxostat vs allopurinol in 512 Chinese patients with gout found similar rates of side effects, liver test abnormalities arising in 3.5% of allopurinol and 2.9% and 1.2% of febuxostat treated subjects; no mention of clinically apparent liver injury).
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    (58 year old man with type 2 dfiabetes and chronic renal failure developed marked serum enzyme elevations within 2 days of starting hemodialysis and switching from allopurinol to febuxostat [ALT rising from 13 to 1134 U/L, Alk P and bilirubin normal], abnormalities resolving within 2 weeks of stopping).
  • Chou HY, Chen CB, Cheng CY, Chen YA, Ng CY, Kuo KL, Chen WL, Chen CH. Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS). J Clin Pharm Ther 2015; 40: 689-92. [PubMed: 26365588]
    (81 year old Taiwanese man developed fever, severe rash, lymphadenopathy and facial edema without eosinophilia 2 days after starting febuxostat [ALT 66 rising to 210 U/L, bilirubin normal], resolving within 3 weeks of stopping).
  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]
    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 8 [0.9%] were attributed to agents used to treat gout, including 7 to allopurinol and 1 to febuxostat [Bohm 2016]).
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    (34 year old man with gout developed jaundice 2 months after adding febuxostat to a regimen of allopurinol and colchicine [bilirubin 8.3 mg/dL, ALT 148 U/L, Alk P 201 U/L] with persistence of injury for over a month at the time of a normal ERCP, but then resolution within 3 weeks of stopping febuxostat).