Background Allopurinol is the most widely used urate-lowering drug (ULD). Drug safety helps, with efficacy and cost, making treatment decisions.
Objectives To analyze the safety of allopurinol in comparison to other ULD
Methods The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library. Selection criteria: a) Patients>18, b) Gout by the ACR criteria or evidence of urate crystal in synovial fluid, c) Comparator (placebo or other ULD), and d) RCTs, cohorts, or meta-analysis. Primary outcomes were: rate of adverse events and death. Quality was assessed with the Jadad’s scale. A meta-analysis with fixed effects was performed.
Results From 544 studies, 7 met the eligibility criteria and were included. All RCT with low power for safety. Participants were similar among studies (all RCTs included a mixed population-gout and hyperuricemia). Allopurinol (max. dose 300mg), was compared to febuxostat (40-240mg) in 5 RCTs, benzbromarone and probenecid in 2 RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26%), followed by allopurinol (11%), and benzbromarone (4%). The incidence of adverse events was similar between allopurinol (range 38.6 to 85) and febuxostat (range 41.8 to 80). Six patients on febuxostat and 3 on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95% CI: 0.98, 1.11) (Fig. 1).
Conclusions Allopurinol is a reasonable safe option, similar or slightly better than other ULDs; although the doses studied may be considered low for some patients.
Disclosure of Interest I. Castrejon: None Declared, E. Toledano: None Declared, M. P. Rosario: None Declared, E. Loza: None Declared, F. Perez-Ruiz Consultant for: Menarini, Ardea Biosciences, Novartis Pharmaceutical Corporation, Savient, L. Carmona: None Declared