Safety Assessment of Povidone K-12 in IV Acetaminophen in Pediatrics.

Background: The potential toxicity of excipients is a recurrent issue in pediatrics, particularly for neonates. The first IV formulation of acetaminophen approved in Canada (Avir Pharma Inc) contains the excipient povidone K-12, which lacks safety data for individuals with immature renal function, specifically, neonates, infants, and those with anuria. Povidone is eliminated by the kidneys and may accumulate in these populations. Objective: To assess the safety of IV povidone K-12 in pediatrics. Methods: The safety of IV povidone K-12 was assessed by first reviewing the available data and then measuring the amount of povidone K-12 exceeding the molecular weight threshold for glomerular filtration (25 000 g/mol). Size exclusion chromatography was used to assess the molecular weight of povidone K-12 to allow estimation of the proportions of povidone K-12 below various molecular weight thresholds. Results: Case reports of povidone accumulation causing organ failure and death in adults were found in the literature. However, the published data were insufficient to assess the risk of accumulation, as no reliable molecular weight determinations could be found. Measurements by chromatography showed that the amount of povidone exceeding the molecular weight threshold of 25 000 g/mol was less than 2 ppm (0.0002%), which suggests a low risk of accumulation despite immature renal function. Conclusions: Povidone K-12 is unlikely to accumulate in neonates, infants, or patients with impaired renal function, with the possible exception of patients with anuria.