PLoS ONE (Jan 2015)

Acute sirolimus overdose: a multicenter case series.

  • Alessandro Ceschi,
  • Elja Heistermann,
  • Sonja Gros,
  • Cornelia Reichert,
  • Hugo Kupferschmidt,
  • Nicholas R Banner,
  • Stephan Krähenbühl,
  • Anne B Taegtmeyer

DOI
https://doi.org/10.1371/journal.pone.0128033
Journal volume & issue
Vol. 10, no. 5
p. e0128033

Abstract

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There are few data relating to sirolimus overdose in the medical literature. Our objectives were to describe all cases of overdose with sirolimus reported to Swiss, German and Austrian Poisons Centres between 2002-2013.An observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose.Five cases of acute sirolimus overdose were reported--three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range.Acute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.