Evaluation of safety and efficacy of febuxostat in patients with severe renal dysfunction

Abstract

[Purpose] It is assumed that the dose of febuxostat does not need to be adjusted even in patients with renal dysfunction. On the other hand, its package insert describes that it should be carefully administered to such patients because of limited experience. We therefore examined its clinical efficacy and adverse events in such patients. [Methods] We retrospectively reviewed the clinical records of 70 patients with chronic kidney disease (CKD) who received febuxostat, excluding those who concomitantly received anti-neoplastic agents and telaprevir, at our hospital between June 2011 and June 2013. Patients were divided into two groups based on the estimated glomerular filtration rate (eGFR) at the time of initiation of febuxostat: the mild-to-moderate group (MM group) consisting of 32 patients with CKD stage 1 to 3, and the severe group (S group) consisting of 38 patients with CKD stage 4 to 5.We compared febuxostat doses, serum uric aãd levels, and other laboratory data including AST, ALT, and CPK levels, drugs administered before febuxostat and concomitantly-administered drugs, and adverse events between the two groups at the initiation of febuxostat and 24 weeks. [Results] The mean dose of febuxostat at 24 weeks was 16.9 and 13.7 mg/day in the MM and S groups, respectively. The mean uric aãd level significantly decreased from 8.7 (before febuxostat) to 6.6 mg/dL (at 24 weeks) and from 9.4 to 6.8 mg/dL in the MM and S groups, respectively. The goal of uric aãd level under 7.0 mg/dL was achieved by 73.3% and 56.5% of the MM and S groups, respectively. Ten patients in the S group experienced adverse events such as CPK elevation or other abnormal laboratory data. However, most of them were mild and transient. [Discussion] Febuxostat could reduce the uric aãd level in the 38 patients with severe CKD and 32 patients with mild-tomoderate CKD at similar doses. No patient had to discontinue febuxostat due to severe adverse effects. Our results suggest that febuxostat at varying dosages can be administered to reduce the uric aãd level even in patients with severe renal dysfunction.