Acute kidney injury associated with febuxostat and allopurinol: a post-marketing study

Abstract

BackgroundFor patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat.MethodsWe carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs).ResultsAmong 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs.ConclusionsAcute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

Factors associated with incidence of acute kidney injury: a Japanese regional population-based cohort study, the Shizuoka study

“…Other variables associated with AKI in our study were approximately consistent with those in previous studies [5,[28][29][30][31]. In contrast with previous reports [30], nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors were not a significant risk factor.…”

Mechanism of Xiezhuo Huayu Yiqi Tongluo Formula in the Treatment of Uric Acid Nephropathy Based on Network Pharmacology, Molecular Docking, and In Vivo Experiments

“…Western therapies have focused on benzbromarone and other drugs to promote uric acid excretion by mediating reabsorption and xanthine oxidase inhibitors such as allopurinol and febuxostat to inhibit uric acid production. However, these drugs have limitations because of their low selectivity and toxicity [16][17][18]. TCMs have unique Evidence-Based Complementary and Alternative Medicine advantages in the treatment of UAN because of the combined characteristics of their multiple components, multiple targets, and multiple pathways.…”

The Singapore Experience With Uncontrolled Gout: Unmet Needs in the Management of Patients

“…Allopurinol and febuxostat have also been associated with acute kidney failure. A post-marketing study reported that the risk of acute renal failure (ARF) was 5.7 and 3.3 times more frequent with febuxostat and allopurinol, respectively, than with other drugs, such as NSAIDs, diuretics, antibiotics, and immunosuppressive therapies [ 72 ]. In a study that enrolled 96 people with an eGFR range of 15-50 ml/min/1.73 m 2 (37.5% were stage 4 CKD patients), febuxostat use up to 80 mg daily did not result in a decline in renal function [ 73 ].…”