Up-titration of allopurinol in patients with gout

Claudine G. Jennings (Lead / Corresponding author), Isla S. Mackenzie, Rob Flynn, Ian Ford, George Nuki, Raffaele De Caterina, Philip L. Riches, Stuart H. Ralston, Thomas M MacDonald, FAST study group

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    43 Citations (Scopus)



    European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels.


    The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients.


    Of 400 patients, 144 (36%) had urate levels =357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal.


    Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients.
    Original languageEnglish
    Pages (from-to)25-30
    Number of pages6
    JournalSeminars in Arthritis and Rheumatism
    Issue number1
    Early online date23 Jan 2014
    Publication statusPublished - Aug 2014


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