title: Acute sirolimus overdose: a multicenter case series.
abstract: BACKGROUND
  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.
  
  
  METHODS
  An observational case-series analysis was performed to determine circumstances, magnitude, management and outcome of sirolimus overdose.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ceschi
authors.affiliation: Berlin Poison Information Centre, Berlin, Germany.
authors.forename: Elja
authors.initials: E
authors.lastname: Heistermann
authors.affiliation: Mainz Poison Control Centre, Mainz, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Gros
authors.affiliation: Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Reichert
authors.affiliation: Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland.
authors.forename: Hugo
authors.initials: H
authors.lastname: Kupferschmidt
authors.affiliation: The Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, Harefield, Middlesex, United Kingdom; National Heart and Lung Institute and Institute of Cardiovascular Medicine and Research, Imperial College, London, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Banner
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University and University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University and University Hospital Basel, Basel, Switzerland.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Taegtmeyer
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D062787:Drug Overdose / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D005334:Fever / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000503:physiopathology; D005759:Gastroenteritis / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects*; D013406:Suicide, Attempted / Q000517:prevention & control*
chemical_list: D002784:Cholesterol; D000469:Alkaline Phosphatase; D020123:Sirolimus