Febuxostat and allopurinol may raise acute kidney injury risk
medwireNews: Febuxostat and allopurinol are associated with an elevated risk for acute kidney injury (AKI), according to study results published in Arthritis Research & Therapy.
The post-marketing study looked at individual case safety reports made to the World Health Organization’s pharmacovigilance database between 2008 and 2018. Febuxostat was associated with 3509 adverse drug reactions (ADRs), of which 317 were AKIs, while allopurinol was associated with 18,730 ADRs, including 1008 AKIs.
Sophie Liabeuf (Amiens University Hospital, France) and colleagues found a 5.67-fold increased risk for AKI in patients who took febuxostat, and a 3.25-fold greater incidence in patients who took allopurinol, compared with those who took other drugs.
The risk for AKI was significantly higher among women than men, with reporting odds ratios (RORs) of 11.60 versus 3.14 among those taking febuxostat, and 4.45 versus 2.29 among those taking allopurinol.
“Due to the potential consequence of AKI in terms of mortality and renal impairment, physicians should take the present signal into account when prescribing febuxostat or allopurinol,” suggest the researchers who highlight that “[u]ntil the present […] study, the risk of AKI associated with allopurinol and febuxostat had been underestimated.”
They emphasize that caution is particularly necessary when prescribing febuxostat or allopurinol to women at risk for AKI, given that the overall mortality rate associated with this outcome was a respective 6.9% and 9.6%.
When the team analyzed specific indications, they found that allopurinol was no longer associated with an increased risk for AKI among those taking it for gout (ROR=0.90), but they suggest that this may be due to a high proportion of missing data for indications.
By contrast, the risk remained a significant 2.53-fold higher for gout patients taking febuxostat compared with other drugs.
Even after excluding drugs known to be associated with AKI in sensitivity analyses, both febuxostat and allopurinol remained associated with an increased risk for AKI, with RORs of 6.34 and 3.64, respectively.
The researchers highlight that not only were these results still statistically significant, but “the signal in the latter analysis was even stronger than in the primary analysis, which reinforces the putative involvement of these drugs in the occurrence of AKI.”
They conclude: “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 Hannah Kitt
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