Up-titration of allopurinol in patients with gout

Semin Arthritis Rheum. 2014 Aug;44(1):25-30. doi: 10.1016/j.semarthrit.2014.01.004. Epub 2014 Jan 23.


Objectives: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Keywords: Allopurinol; Clinical guidelines; Gout; Prescribing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Allopurinol / administration & dosage
  • Allopurinol / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gout / drug therapy*
  • Gout Suppressants / administration & dosage
  • Gout Suppressants / therapeutic use*
  • Humans
  • Male
  • Middle Aged


  • Gout Suppressants
  • Allopurinol