title: Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions.
abstract: OBJECTIVE
  Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO) activity, remains the standard for pharmacologic urate-lowering management of gout. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol adverse reactions (AE) occur much less frequently, and include severe cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol hypersensitivity syndrome. During clinical development of febuxostat (FEB), a recently approved non-purine analog inhibitor of XO, subjects with severe allopurinol intolerance were excluded from randomized double-blind FEB/allopurinol comparative trials.
  
  
  METHODS
  In this retrospective study, safety and urate-lowering efficacy of FEB was assessed in 13 successively encountered gout patients with prior documented severe allopurinol reactions.
  
  
  RESULTS
  FEB was well tolerated in 12 of 13 patients, each of whom remains on treatment. One patient previously hospitalized with documented exfoliative erythroderma during allopurinol treatment, developed biopsy-confirmed cutaneous leukocytoclastic vasculitis. None of the other 12 patients treated with FEB showed rash, worsening hepatic function, blood cytopenia or eosinophilia.
  
  
  CONCLUSIONS
  In 12 of our 13 gout patients with previously documented severe allopurinol AE, FEB treatment was safe. However, the development of a hypersensitivity type cutaneous vasculitis (likely but not definitively FEB-related) early in treatment mandates caution, careful dose escalation, and close monitoring when FEB urate-lowering therapy of allopurinol-intolerant patients is considered.
authors: University of Chicago Medical Center, 5841 S. Maryland Ave., MC 0930, Chicago, IL 60637, USA. schohan@medicine.bsd.uchicago.edu
authors: Saima
authors: S
authors: Chohan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000592:standards; D000069465:Febuxostat; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006074:Gout Suppressants / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol