Association between an excess risk of acute kidney injury and concomitant use of ibuprofen and acetaminophen in children, retrospective analysis of a spontaneous reporting system

Abstract

Purpose: Ibuprofen and acetaminophen are frequently alternated or simultaneously used to treat fever or pain in children, while the evidence for the safety of such a combination is lacking. In this study, we analyzed the association of acute kidney injury (AKI) with ibuprofen, acetaminophen, and the combination of both drugs in children (0-12 years) by using the FDA Adverse Event Reporting System (AERS) database between January 2004 and June 2012. Methods: Adverse event reports in children aged 0 to ≤12 years were included in the study. Cases were defined as reports of AKI according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology, non-cases as all other reports. Exposure categories were divided into three index groups: two groups where ibuprofen or acetaminophen were used in absence of one another and another group where both drugs were used concomitantly. There was also a reference group, in which neither ibuprofen nor acetaminophen was used. These index groups were compared with the reference group using reporting odds ratios (RORs). Results: In total, 47,803 reports were included in the study. After adjusting for year of reporting, age, and sex, the ROR for an AKI in children who used only ibuprofen or acetaminophen compared with children who used neither ibuprofen nor acetaminophen was 2.14 (95 % CI: 1.59-2.88) and 1.53 (95 % CI: 1.18-1.97), respectively, while the adjusted ROR was 4.01 (95 % CI: 2.96-5.43) when both drugs were concomitantly used. Conclusions: The results illustrate that the concomitant use of ibuprofen and acetaminophen in children might be associated with increased risk of AKI. © 2014 Springer-Verlag.