Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.
Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.
Department of Clinical Pharmacology and Toxicology, University and University Hospital Basel, Basel, Switzerland ; University Clinic of Internal Medicine, Kantonspital Baselland Liestal, Liestal, Switzerland.
Claudia
C
Gregoriano
Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland ; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
Alessandro
A
Ceschi
Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland.
Christine
C
Rauber-Lüthy
Swiss Toxicological Information Centre, Associated Institute of the University of Zurich, Zurich, Switzerland.
Hugo
H
Kupferschmidt
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.
Nicholas R
NR
Banner
Department of Clinical Pharmacology and Toxicology, University and University Hospital Basel, Basel, Switzerland.
Stephan
S
Krähenbühl
Department of Clinical Pharmacology and Toxicology, University and University Hospital Basel, Basel, Switzerland.
Anne B
AB
Taegtmeyer
D000328:Adult; D000553:Ambulatory Care / Q000706:statistics & numerical data; D000963:Antimetabolites / Q000506:poisoning*; D001379:Azathioprine / Q000506:poisoning*; D002606:Charcoal / Q000627:therapeutic use*; D002675:Child, Preschool; D062787:Drug Overdose / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005751:Gastric Lavage; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000506:poisoning*; D011039:Poison Control Centers; D012189:Retrospective Studies; D013557:Switzerland
D000963:Antimetabolites; D002606:Charcoal; D015122:Mercaptopurine; D001379:Azathioprine