Benzbromarone 50mg tablets

ObjectivesTo assess the incidence and risk of nephrolithiasis in people receiving uricosuric therapies for gout.MethodsA search was conducted using MEDLINE, Embase, Cochrane Library, Web of Science and Clinical Trials.gov electronic databases on 16 May 2023 (updated 10 May 2024). Randomized controlled trials (RCTs) and cohort studies assessing the incidence and/or risk of nephrolithiasis in adults with gout treated with uricosuric therapies were included (with or without a non-uricosuric urate-lowering therapy [ULT] comparator group). Other designs and studies involving people with asymptomatic hyperuricaemia only were excluded. A random-effects model was used to calculate pooled incidence and risk estimates. Risk of bias assessments were performed for all included studies.ResultsTwenty-three studies (10 RCTs, 13 cohort studies) were included in the meta-analysis (n = 78 042 participants, 15 385 received a uricosuric). The pooled incidence of nephrolithiasis amongst participants taking uricosuric therapies was 3.35% (95% CI 2.03-4.92) (Benzbromarone [10 studies] 3.92% [1.89-6.52], Lesinurad [6 studies] 3.08% [1.38-5.38]). Pooled incidence by study design was 2.87% (95% CI 1.30-4.93) in 10 RCTs and 3.93% (1.95-6.44) in 13 cohort studies. The pooled risk ratio for nephrolithiasis in participants taking uricosuric therapies vs participants not taking a uricosuric (other ULT and/or placebo) (nine studies) was 1.63 (95% CI 1.33-2.00, P = 0.001).ConclusionNephrolithiasis is a common side effect of uricosuric therapies, although the quality of evidence for this is low-moderate due to significant heterogeneity and bias. Further research is required to identify those at highest risk, and who may benefit from additional interventions such as urinary alkalinization. Our estimates of incidence of nephrolithiasis and associated risk can lead to more informed shared treatment decisions in the management of gout.

Abstract licence: CC BY

BackgroundBenzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares.Main body of the abstractThrough several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product’s withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product’s marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use.Short conclusionBenzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.

Abstract licence: CC BY 4.0