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

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

Article highlights

• Urate-lowering drugs have largely different safety and tolerability profiles.

• Among xanthine oxidase inhibitors, allopurinol may produce a mild skin rash and severe cutaneous reactions, while febuxostat is usually better tolerated.

• More evidence is required to define the safety profile of topiroxostat, arhalofenate, tranilast, and sulfinpyrazone.

• There are some unanswered questions about the pharmacological interactions of probenecid and the hepatotoxicity of benzbromarone.

• Combination therapy with lesinurad or verinurad and XOI is infrequently accompanied by side effects.

• Rasburicase and pegloticase are usually well tolerated with some specific exceptions.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed they have received grants from Pfizer and have served on advisory boards for Novartis, Horizon Pharma, Proteo Thera, Selecta Biosciences, Olatec, IFM Therapeutics, and Mallinckrodt Pharmaceuticals. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.