Benzbromarone in the treatment of gout

Abstract

Background: Benzbromarone 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 abstract: Through 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 Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to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 conclusion: Benzbromarone 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.

Effects of Urate-Lowering Therapy on Risk of Hyperlipidemia in Gout by a Population-Based Cohort Study and on In Vitro Hepatic Lipogenesis-Related Gene Expression

“…Benzbromarone, sulfinpyrazone, and probenecid lower serum UA levels by increasing renal urate excretion. Benzbromarone is not available in many countries because of concerns about its hepatotoxicity, and it is not recommended for patients with liver and renal dysfunction [ 46 ]. This risk could be reduced by increasing the dose gradually and monitoring liver function.…”

Hyperuricemia, the heart, and the kidneys – to treat or not to treat?

“…It inhibits the apical urate exchanger in proximal tubules, which reduces urate reabsorption and lowers serum levels. Additionally, uricosurics are contraindicated when an estimated glomerular filtration rate (eGFR)<50 mL/min, which limits their use in CKD, although some studies have been done for testing their efficacy and safety profile [32][33][34][35][36][37]. Recently, a novel agent called pegloticase, a pegylated recombinant mammalian urate oxidase, has been developed.…”

Association between Gout, Urate-Lowering Therapy, and Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study

“…Xanthine oxidase inhibitor (XOI) blocks the synthesis of UA, and an XOI, allopurinol, has been used globally for the treatment of gout patients with renal or cardiovascular disease (CVD) comorbidity, as a first-line medication [ 16 ]. Uricosuric drugs, including benzbromarone, sulfinpyrazone, and probenecid, which are second-line gout therapies, block renal tubular urate reabsorption [ 17 ]. They act predominantly on urate anion exchanger 1, an organic anion transporter, to prevent the reuptake of UA at the proximal renal tubule, which increases UA renal excretion [ 17 ].…”

“…Uricosuric drugs, including benzbromarone, sulfinpyrazone, and probenecid, which are second-line gout therapies, block renal tubular urate reabsorption [ 17 ]. They act predominantly on urate anion exchanger 1, an organic anion transporter, to prevent the reuptake of UA at the proximal renal tubule, which increases UA renal excretion [ 17 ]. Although gout prevalence is high in Taiwan, in addition to the presence of definitive ULT, physicians largely overlook gout during primary care [ 18 ].…”