title: Up-titration of allopurinol in patients with gout.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK. Electronic address: claudine@memo.dundee.ac.uk.
authors.forename: Claudine G
authors.initials: CG
authors.lastname: Jennings
authors.affiliation: Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK.
authors.forename: Isla S
authors.initials: IS
authors.lastname: Mackenzie
authors.affiliation: Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Flynn
authors.affiliation: University of Glasgow, Robertson Centre for Biostatistics, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: Western General Hospital, Centre for Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: George
authors.initials: G
authors.lastname: Nuki
authors.affiliation: Cardiovascular Division, G d'Annunzio University, SS. Annunziata Hospital, and Center of Excellence on Aging (Ce.S.I), Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Western General Hospital, Centre for Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Riches
authors.affiliation: Western General Hospital, Centre for Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.affiliation: Medicines Monitoring Unit (MEMO), University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: MacDonald
mesh_terms: D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D006074:Gout Suppressants; D000493:Allopurinol
keywords: Allopurinol; Clinical guidelines; Gout; Prescribing