OBJECTIVES: 1) To investigate ECG changes following co-proxamol (paracetamol 325 mg and dextropropoxyphene 32.5 mg) overdose in comparison to co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine) in a prospective study. 2) To examine the relationship between estimated dextropropoxyphene dose and ECG changes in a larger patient population. BACKGROUND: Co-proxamol is a common cause of drug-induced death and hospital admission in the United Kingdom. ECG changes following dextropropoxyphene have been reported in animals and man, including QRS prolongation. METHODS: The prospective study was conducted on 15 patients and controls with overdose. A retrospective study of a cohort of 159 co-proxamol overdoses from a combined data set from Edinburgh and Newcastle, Australia was also conducted. The measured or estimated "four hour" plasma paracetamol level was used as a surrogate of the amount of dextropropoxyphene ingested. RESULTS: In the prospective study co-proxamol overdose caused statistically significant QRS prolongation (mean [95% CI] 99.36 [96.19, 102.53] msec), compared to the other combination opioid-paracetamol products (82.84 [80.81, 84.88] msec) but no effect on PR or QTc. QRS duration increase was evident soon after exposure and remained prolonged and stable over the following 24 h. In the retrospective cohort study a dose dependency of effect on QRS was documented, although the correlation coefficient relating paracetamol level to effect was relatively weak (r = 0.338, Sig. [2-tailed] 0.003, n = 74). CONCLUSIONS: QRS is significantly prolonged in co-proxamol overdose, and this prolongation is dose dependent. These findings have clinical relevance to the management of patients with co-proxamol poisoning.
OBJECTIVES: 1) To investigate ECG changes following co-proxamol (paracetamol 325 mg and dextropropoxyphene 32.5 mg) overdose in comparison to co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine) in a prospective study. 2) To examine the relationship between estimated dextropropoxyphene dose and ECG changes in a larger patient population. BACKGROUND:Co-proxamol is a common cause of drug-induced death and hospital admission in the United Kingdom. ECG changes following dextropropoxyphene have been reported in animals and man, including QRS prolongation. METHODS: The prospective study was conducted on 15 patients and controls with overdose. A retrospective study of a cohort of 159 co-proxamol overdoses from a combined data set from Edinburgh and Newcastle, Australia was also conducted. The measured or estimated "four hour" plasma paracetamol level was used as a surrogate of the amount of dextropropoxyphene ingested. RESULTS: In the prospective study co-proxamoloverdose caused statistically significant QRS prolongation (mean [95% CI] 99.36 [96.19, 102.53] msec), compared to the other combination opioid-paracetamol products (82.84 [80.81, 84.88] msec) but no effect on PR or QTc. QRS duration increase was evident soon after exposure and remained prolonged and stable over the following 24 h. In the retrospective cohort study a dose dependency of effect on QRS was documented, although the correlation coefficient relating paracetamol level to effect was relatively weak (r = 0.338, Sig. [2-tailed] 0.003, n = 74). CONCLUSIONS: QRS is significantly prolonged in co-proxamoloverdose, and this prolongation is dose dependent. These findings have clinical relevance to the management of patients with co-proxamolpoisoning.
Authors: Wayne A Ray; Katherine T Murray; Vivian Kawai; David J Graham; William O Cooper; Kathi Hall; Charles Michael Stein Journal: Pharmacoepidemiol Drug Saf Date: 2013-02-14 Impact factor: 2.890