Many AKI Reports in FAERS Linked to Drugs Not Recognized as Nephrotoxic
Acute kidney injury (AKI) was found to be a common reason for reporting in the Food and Drug Administration Adverse Event Reporting Database (FAERS), however most of these reports were linked to drugs not typically recognized as nephrotoxic, according to a study published in Pharmacotherapy.
To identify the medications most commonly reported for AKI, researchers conducted a retrospective pharmacovigilance disproportionality analysis using the FAERS database (Q1 2004 to Q3 2015). These drugs were categorized as known, possible, or new nephrotoxins based on published resources (i.e, drug information databases, reference books, review articles). Using the reporting odds ratio (ROR), the authors quantified the association between these medications and AKI; an ROR >1 indicated that the drug was more likely to be reported for AKI than for other adverse reactions.
A total of 7,241,385 reports were included in the analysis; 2.7% (193,996) of these reports involved AKI. The majority of AKI reports were associated with new potential nephrotoxins (64.8%), followed by possible nephrotoxins (18.6%) and known nephrotoxins (16.5%). The 20 most frequently reported new potential nephrotoxins included aprotinin, metformin, zoledronic acid, lenalidomide, dabigatran, deferasirox, adalimumab, atorvastatin, alendronate, everolimus, etanercept, digoxin, sunitinib, exenatide, bevacizumab, telaprevir, rosuvastatin, bortezomib, imatinib, and aliskiren.
Aprotinin was associated with over 7,000 reports and had the highest ROR (115.70, 95% CI, 110.63-121.01), followed by sodium phosphate (ROR 55.81, 95% CI, 51.78‐60.17), furosemide (ROR 12.61, 95% CI, 11.94‐13.32), vancomycin (ROR 12.19, 95% CI, 11.45‐12.99), and metformin (ROR 10.65, 95% CI, 10.31‐11.00). Combined RORs were also calculated for the 20 most commonly reported drugs within each classification: known nephrotoxins (ROR 3.71, 95% CI, 3.66-3.76), possible nephrotoxins (ROR 2.09, 95% CI, 2.06-2.12), and new potential nephrotoxins (ROR 1.55, 95% CI, 1.53-1.57).
RORs were generally found to be higher for drugs known to be nephrotoxic, however, in some, cases, the database failed to show greater odds of reporting for an agent known to cause AKI (i.e., celecoxib: ROR 0.92; naproxen: ROR 0.63). "When interpreting these results, it is important to consider that the ROR describes the odds that the adverse event was reported and not the odds that it occurred," explained the authors.
Despite the study's limitations, the authors concluded that the "report provides data on medications needing further research to determine the risk of AKI with these new potential nephrotoxins."
For more information call or visit wiley.com.