Febuxostat in severe renal impairment

The problem with newer agents is that there are gaps in the knowledge about its use in settings where older agents have shown benefit. To merely extend observations without evidence is no assurance that the same benefit would be seen.

One example is febuxostat in gout. When it was launched in the Philippines back in 2010, speakers emphasized that while dose adjustments are not needed in moderate renal insufficiency (eGFR>=60ml/min) there was no data yet for severe CKD. Allopurinol needed to be adjusted in moderate CKD and, with the gingerly titration schedule (starting with 50mg OD then increase by 50mg every 2-4 weeks), I always wondered if ever a target SUA is reached this way. However, there is data (albeit, non RCT) for Allopurinol in severe renal impairment and it has been our go to drug in this setting if without contraindications (like SJS or AHS).

Personally, I believe that the “no dose adjustment needed in moderate CKD” label suggests a better renal safety profile for febuxostat compared to allopurinol. I’ve been using it for some patients with eGFR>=30ml/min and I’ve yet to run into problems. But I use a more careful approach – starting with 20 mg QD (Yes, it is available in the Philippines despite no studies about its use in trials) increasing the dose to 40mg QD if SUA is not yet on target. I’m happy to note that many of my patients reach SUA<=6mg/dl with a few patients reaching only <=7mg/dl. But with this study, I’ve gained confidence to go higher – probably up to 60mg QD. And I’ve gotten data to try it in patients with an ever lower eGFR (up to 15ml/min). In patients with normal renal function, febuxostat can be given up to 120mg QD based on US FDA recommendations (and 240mg QD according to the EMA).

Am I worried about the high treatment emergent AEs cited in the study? If you compare across groups, the highest AE rates (87.5%) were observed in the 40/80mg QD group but those getting 60mg/day had the same AE rates (78.1%) as placebo. That’s why, I’d only be confident raising the dose to 60mg/ day. And most of these AEs were due to the underlying renal problem and not judged to be because of the intervention.

Febuxostat is a non-pyrimidine xanthine oxidase inhibitor used in the treatment of hyperuricemia in gout. Due to differences in structure, it was initially offered as an alternative for patients intolerant of or those who develop adverse events to allopurinol. Guidelines at that time reflected such. But the latest recommendations have been revised to reflect that it can be first line therapy and not merely an alternative. Typical adverse events associated with Febuxostat are similar to those of Allopurinol – GI upset, liver function abnormalities and rashes.

Disclosure: I was part of the speakers bureau for Febuxostat from 2010-2014 and had received honoraria from industry.

[Impact of Febuxostat on Renal Function in Gout Subjects with Moderate-to-Severe Renal Impairment. – PubMed – NCBI] http://www.ncbi.nlm.nih.gov/pubmed/26894653

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