Valderilio Feijó Azevedo1,2, Igor Age Kos3, Ana Beatriz Vargas-Santos4, Geraldo da Rocha Castelar Pinheiro4, Eduardo Dos Santos Paiva5. 1. Universidade Federal do Paraná, Rua General Carneiro 181, Centro, Curitiba, Paraná, Brazil. valderilio@hotmail.com. 2. Edumed Educação em Saúde, Rua Bispo Dom José, 2495, Curitiba, Paraná, Brazil. valderilio@hotmail.com. 3. Edumed Educação em Saúde, Rua Bispo Dom José, 2495, Curitiba, Paraná, Brazil. 4. Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil. 5. Universidade Federal do Paraná, Rua General Carneiro 181, Centro, Curitiba, Paraná, Brazil.
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. 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 Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to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.
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. 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.
Authors: Yuhua Wang; Ram Naresh Pandey; Kaushik Roychoudhury; David Milewski; Tanya V Kalin; Sara Szabo; Joseph G Pressey; Rashmi S Hegde Journal: Mol Cancer Ther Date: 2021-03-01 Impact factor: 6.009