Indications For Acetylcysteine After Intentional Paracetamol Overdose: Comparison of. Methods Based Upon Reported Dose Versus Serum Concentrations.
Proceedings of the British Pharmacological Society at http://www.pA2online.org/abstracts/Vol10Issue4abst164P.pdf
Indications For Acetylcysteine After Intentional Paracetamol Overdose: Comparison of Methods Based Upon Reported Dose Versus Serum Concentrations S. Bisma Fatima, Nayab Shah, W. Stephen Waring. York Hospital, York, UK
Background The Medicines and Healthcare products Regulatory Agency (MHRA) have recently issued a safety update regarding acetylcysteine. A single nomogram is now used to determine paracetamol exposure after acute ingestion, which replaces the ‘standard’ and ‘high risk’ treatment lines. After staggered overdose, acetylcysteine is indicated after more than >150 mg/kg, or >75 mg/kg in patients with additional risk factors. However, the MHRA propose abandoning risk factor assessment, and this raises concern over what threshold paracetamol dose would be most appropriate indicator for acetylcysteine in the context of staggered overdose. Aims The present study sought to examine the relationship between stated paracetamol dose and analytical confirmation of drug concentrations, and to evaluate the performance of various dose thresholds for predicting the occurrence of potentially toxic paracetamol concentrations, as defined by the treatment nomogram. Methods Patients admitted to York Hospital due to paracetamol overdose were studied between January 2011 and May 2012. Inclusion criteria were acute ingestion at a single time-point, and paracetamol concentration determined between 4-15 hours. Data examined were patient weight, stated paracetamol dose, interval between overdose and paracetamol concentration, and whether paracetamol concentration was higher than the treatment nomogram between 4 and 15 hours after acute ingestion. Data are presented as median (interquartile range). Results There were 534 patients; inclusion criteria were met in 122 (81 women, 66%). Median paracetamol dose was 16 g (10-22 g), equivalent to 218 mg/kg (123-309 mg/kg), and serum paracetamol concentrations were higher than the treatment nomogram in 67 (54.9%). Stated dose (as mg/kg) was predictive of potentially toxic paracetamol concentrations: receiver operating characteristic AUC 0.70 (P
