Safety Assessment of Povidone K-12 in IV Acetaminophen in Pediatrics
Bibliographic record
Abstract
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. Keywords: excipient, toxicity, acetaminophen, pain, povidone, povidone storage disease RÉSUMÉ Contexte : La toxicité potentielle des excipients est un problème fréquent en pédiatrie, en particulier chez les nouveau-nés. La première formulation IV de l’acétaminophène approuvée au Canada (Avir Pharma Inc) contient l’excipient povidone K-12, pour lequel il n’existe pas de données d’innocuité chez les personnes dont la fonction rénale est immature, notamment les nouveau-nés, les nourrissons et les patients anuriques. La povidone est éliminée par les reins et peut s’accumuler chez ces populations. Objectif : Évaluer l’innocuité de la povidone K-12 (IV) en pédiatrie. Méthodologie : L’innocuité de la povidone K-12 intraveineuse a été évaluée en examinant les données disponibles et en mesurant la quantité de povidone K-12 dépassant le seuil de la masse moléculaire de la filtration glomérulaire (25 000 g/mol). La chromatographie d’exclusion stérique a été utilisée pour déterminer la masse moléculaire de la povidone K-12 afin d’estimer les proportions de povidone K-12 en dessous de différents seuils de masse moléculaire. Résultats : Des cas d’accumulation de povidone ayant causé une défaillance des organes et le décès chez des adultes ont été trouvés dans la littérature. Cependant, les données publiées ne permettaient pas d’évaluer le risque d’accumulation, car aucune détermination fiable de la masse moléculaire n’était disponible. Les mesures par chromatographie ont montré que la quantité de povidone dépassant le seuil de masse moléculaire de 25 000 g/mol était inférieure à 2 ppm (0,0002 %), ce qui laisse supposer un faible risque d’accumulation, malgré une fonction rénale immature. Conclusions : Il est peu probable que la povidone K-12 s’accumule chez les nouveau-nés, les nourrissons ou les patients ayant une insuffisance rénale, à l’exception possible des patients anuriques. Mots-clés : excipient, toxicité, acétaminophène, douleur, povidone, accumulation de la povidone
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".