Acute Thiopurine Overdose: Analysis of Reports to a National Poison Centre 1995–2013

Abstract

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.

Testicular Alteration in Over Dosage of Azathioprine: A Histological and Histochemical Study in Wistar Rats

“…The maximum licensed dose for oral AZA is 5 mg/kg/day in individuals (Gregoriano et al, 2014). Tolerance of large single doses of azathioprine have been reported as the patient showed no relevant symptoms apart from vomiting, slight decrease in white blood cell count and marginal changes in liver function parameters (Carney et al, 1974, Chow et al, 2004.…”

Acute toxicity profile of tolperisone in overdose: Observational poison centre-based study

“…Tolperisone has a molecular weight of 281.8 Dalton, meaning that it is expected to be readily adsorbed into the 10-1000 Å-sized charcoal pores of current activated charcoal products. 17 The fact that gastrointestinal decontamination was performed in children more frequently than in adults, as we already found in two other studies from our centre, 18,19 possibly reflects the earlier presentation of children to emergency services and the difficulty medical staff have in obtaining an accurate account of the amount of drug ingested. In any case, due to the rapid onset of lifethreatening neurological, respiratory, and cardiovascular symptoms in some cases, the prompt initiation of emergency measures, even in the out-of-hospital setting, seems even more important than gastrointestinal decontamination procedures.…”

Accidental Poisoning With 6-MP in a Sibling of Pediatric Patient Treated With Maintenance Chemotherapy

“…2 Poisoning following oral chemotherapy has been seldom reported in children with only 13 6-MP poisoning cases published. [3][4][5][6] Five cases were due to prescription negligence 6 and 7 cases occurred in children. Among them, 5 concerned a poisoning at home but only 2 cases were similar to ours.…”