FDA strengthens acute kidney injury warnings for J&J’s Invokana (canagliflozin) and AZ’s Farxiga (dapagliflozin) – June 14, 2016

The FDA released a Drug Safety Communication today strengthening the existing warnings for J&J’s Invokana (canagliflozin) and AZ’s Farxiga (dapagliflozin) about the risk of acute kidney injury. The announcement advises patients to seek immediate medical attention if they experience symptoms of acute kidney injury. It advises providers to consider potential predisposing factors for acute kidney injury and assess kidney function prior to starting treatment with either drug, monitor periodically thereafter, and promptly discontinue treatment if symptoms appear. This warning was based on a search of the FDA Adverse Event Reporting System showing 101 confirmable cases of acute kidney injury with the two drugs between March 2013 and October 2015. Following the warning, J&J noted that the May 2016 label updates for Invokana and Invokamet (canagliflozin/metformin) included language reflecting this stronger warning. There was no mention of Lilly/BI’s Jardiance (empagliflozin) in the announcement, and the just-released positive microvascular results from the EMPA-REG OUTCOME trial found no increased risk of acute kidney injury with the drug and positive long-term effects on renal outcomes. This discrepancy suggests that there could be within-class differences in the effect of SGLT-2 inhibitors on the kidneys, which would be surprising at this stage given how homogenous the class is typically considered to be. Results from the ongoing outcomes trials for J&J’s Invokana and AZ’s Farxiga should help clarify this question; there could potentially be difficult tradeoffs for clinicians if those trials find both an increased risk of acute kidney injury and a reduced risk of long-term cardiovascular and/or renal outcomes with the drugs. It is too early to speculate but we wanted to alert readers to this strengthened warning. We welcome opinions on this subject – please share your view that we will keep anonymous but that will contribute to our understanding of to what degree this may will impact the field.

-- by Emily Regier and Kelly Close