Safety of Ibuprofen in Children With G6PD Deficiency: A Systematic Review

Abstract

Introduction: Ibuprofen is included on websites and frequently referenced lists as medium risk for inducing hemolysis in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This presents a challenge for otolaryngologists who perform tonsillectomy and other surgeries in children, as ibuprofen serves as an important alternative to opioids for perioperative pain control. We systematically review published literature and national medication databases to evaluate the risk of hemolytic anemia and related complications when ibuprofen is used in children with G6PD deficiency.Methods: Systematic literature review using preferred reporting items for systematic reviews and meta-analyses methodology. National drug adverse reaction database inquiry.Results: Our search yielded 774 results for review consideration. Of these, three studies were included in our final analysis (two retrospective case-series, and one nonrandomized prospective study). The prospective study showed no evidence of hemolysis from perioperative exposure to ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs) in children with G6PD deficiency at high risk. Two population studies in the Middle East suggested extremely low incidence of ibuprofenrelated hemolysis (approximate 1/100,000 affected children per year). United States Food and Drug Administration (FDA), European Medicine Agency, and Health Canada adverse drug reaction databases reveled reported ibuprofen-related hematologic adverse reactions of approximate 1/100 million affected children per year.Conclusions: There is scant, low-quality evidence of hemolytic anemia caused by ibuprofen in children with G6PD deficiency. If an association does exist, it is extremely rare. Drug-induced hemolytic anemias are recognizable and reversible following discontinuation of the inciting medication. Given these low risks, ibuprofen should be considered an appropriate choice in the management of perioperative pain in children with G6PD deficiency.