Safety and tolerability of available urate-lowering drugs: a critical review

Expert Opin Drug Saf. 2019 Apr;18(4):261-271. doi: 10.1080/14740338.2019.1594771. Epub 2019 Mar 27.

Abstract

Introduction: Urate-lowering therapy (ULT) is the cornerstone of gout management, which is a widespread chronic illness characterized by hyperuricemia, arthropathy, tophus development, and urolithiasis. Since asymptomatic increased serum urate levels are associated with a higher risk of cardiovascular, renal and metabolic disorders, a larger use of ULTs in the general population is expected in the near future.

Areas covered: This review will focus on the safety and tolerability profile of the available urate-lowering drugs: xanthine oxidase inhibitors (XOIs), uricosuric agents and injectable uricases.

Expert opinion: Older drugs for ULT like allopurinol are well studied and extensively described from typical adverse effects (mild skin rash) to unusual fatal reactions, while febuxostat seems to be overall well tolerated. More evidence is required to define the safety profile of topiroxostat, arhalofenate, tranilast, and sulfinpyrazone. Furthermore, there are some unanswered questions about the pharmacological interactions of probenecid and the hepatotoxicity of benzbromarone. Despite a limited use in clinical practice, combination therapy with lesinurad or verinurad and XOI is not frequently accompanied by side effects. Rasburicase and pegloticase are usually well tolerated with some specific exceptions. Before prescribing UL drugs, physicians should take into account their safety profile tailoring the treatment on the patient characteristics.

Keywords: Allopurinol; benzbromarone; febuxostat; gout; lesinurad; pegloticase; probenecid; rasburicase; safety.

Publication types

  • Review

MeSH terms

  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology
  • Gout / drug therapy
  • Gout Suppressants / adverse effects
  • Gout Suppressants / pharmacology*
  • Humans
  • Uric Acid / metabolism*
  • Uricosuric Agents / adverse effects
  • Uricosuric Agents / pharmacology*
  • Xanthine Oxidase / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Gout Suppressants
  • Uricosuric Agents
  • Uric Acid
  • Xanthine Oxidase