Renal failure reported more often with allopurinol, febuxostat
Reports of acute renal failure occur 5.7 times more frequently among patients treated with febuxostat, and 3.3 times more often with allopurinol, compared with other drugs, according to data published in Arthritis Research & Therapy.
“Drugs constitute one of the leading causes of acute kidney injury (AKI),” Amayelle Rey, PhD, of Amiens University Hospital in France, and colleagues wrote. “The prevalence of drug-induced AKI has increased in recent years — especially in intensive care units. ... Although [urate-lowering therapies] have sometimes been presented as reno-protective by targeting hyperuricemia, renal risks associated with allopurinol or febuxostat have rarely been evaluated, especially in post-marketing studies.”
To analyze the renal risk associated with febuxostat and allopurinol, Rey and colleagues conducted a disproportionality analysis of acute renal failure with both drugs using the WHO’s VigiBase pharmacovigilance database. The researchers examined individual case safety reports of suspected adverse drug interaction within the database between Jan. 1, 2008, and Dec. 31, 2018. Out of more than 9 million reports in adult patients of known age and gender reported to the database during that time, 3,509 involved febuxostat and 18,730 included allopurinol.
Rey and colleagues analyzed the frequencies of acute renal failure reports, as a standardized Medical Dictionary for Regulatory Activities query, for allopurinol and febuxostat, and compared them with those of all other adverse drug interactions. The researchers evaluated the stability of their results using a series of sensitivity analyses.
According to the researchers, there were 317 cases of acute renal failure connection with febuxostat and 1,008 involved with allopurinol. Acute renal failure was reported significantly more often for both febuxostat (reporting OR = 5.67; 95% CI, 5.05-6.36) and allopurinol (reporting OR = 3.25; 95% CI, 3.05-3.47).
In addition, the reporting odds ratio for both drugs was higher among women, at 11.6 (95% CI, 9.74-13.82) compared with 3.14 (95% CI, 2.69-3.67) among men for febuxostat, and 4.45 (95% CI, 4.04-4.91) compared with 2.29 (95% CI, 2.11-2.5) for allopurinol. The subsequent sensitivity analyses confirmed the disproportionality for each drug.
“Due to the potential consequences of AKI in terms of mortality and renal impairment, physicians should take the present signal into account when prescribing febuxostat or allopurinol,” Rey and colleagues wrote. “Pharmacovigilance databases are very valuable tools for post-marketing surveillance and can be also used to monitor treatment effectiveness in phase IV clinical studies. Our present results pave the way for randomized phase IV trials designed to assess the likely causal relationship between AKI and febuxostat or allopurinol.” – by Jason Laday
Disclosure: The authors report no relevant financial disclosures.