Febuxostat in chronic gout

• febuxostat is a non-purine selective inhibitor of xanthine oxidase that achieves its therapeutic effects by decreasing the serum uric acid concentration
  • most common side effects associated with febuxostat are diarrhoea, nausea, headache, liver function test abnormalities and rash
  • uncommon side effects include fatigue, oedema, dizziness, altered sense of taste, increase in blood amylase, decrease in platelet count, increase in blood creatinine, and arthralgia
  • rare side effects include nervousness, insomnia, asthenia and renal insufficiency
  • summary of product characteristics (SPC) states that treatment with febuxostat is not recommended for people with ischaemic heart disease or congestive heart failure
    • for full details of side effects and contraindications, see the SPC
• NICE have stated that febuxostat, within its marketing authorisation, is recommended as an option for the management of chronic hyperuricaemia in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated

Notes:

• in the CARES study
  • in patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol (2)
• the MHRA states there is an increased risk of cardiovascular death and all-cause mortality in clinical trial in patients with a history of major cardiovascular disease
  • avoid treatment with febuxostat in patients with pre-existing major cardiovascular disease (for example, myocardial infarction, stroke, or unstable angina), unless no other therapy options are appropriate (3)
  • caution is required if prescribing febuxostat in patients with pre-existing major cardiovascular disease, particularly, in those with evidence of high urate crystal and tophi burden or those initiating urate-lowering therapy (4)
• comparing allopurinol and febuxostat (5):
  • allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease

Reference:

• 1. NICE (December 2008). Febuxostat for the management of hyperuricaemia in people with gout
• 2. White WB et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018 Mar 18; 378:1200-1210
• 3. MRHA (July 2019).Drug Safety Update.
• 4. Drug Safety Update volume 16, issue 10: May 2023: 3
• 5. O'Dell JR et al.Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management NEJM Evid 2022; 1 (3) DOI:https://doi.org/10.1056/EVIDoa2100028