the first 20 h. with normal Osmotic renal diuresis was function observed was which led to effective moderately and safe. severe dehydration. Jobard, et al. Both patients The 30 yr old Data from Methylpyrazole intubated, man recovered these 2 and ventilation; 30 yr from coma in 48 patients haemodialysis in old man given IV h, anuria and suggested ethylene glycol loading dose of 10 haemodialysis that in cases poisoning.” mg/kg 4MP, then given for 8 days; of severe EG Clinical haemodialysis hospital stay of poisoning Toxicology, started; between 14 days and with toxic 34(4), 373-377 4-6hr of dialysis, complete plasma EG (1996). infusion of 2.5 recovery levels and mg/kg/h of 4MP observed. renal failure, Reported as given to a 4MP S12 in the The 50yr old compensate for loading dose dossier man had flat loss of 4MP in of EEG and QRS dialysate. The complexes 50yr old man given followed by with severe 4MP loading dose continuous acidosis, anuria of 20mg/kg, one hr infusion of 1 on admission, later to despite haemodialysis 1.5mg/kg/h symptomatic started and during the treatment- he maintenance dose hrs of had of 4MP haemodynamic 1.5mg/kg/h may be instability and infused during effective. died 48hr after haemodialysis. admission due to multiorgan failure and disseminated intravascular coagulation. Secondary pharmacodynamic effects Not evaluated. Time course of pharmacodynamic effects In the study reported by McMartin, 2012 (in healthy subjects, the time above the presumed minimum effective concentration of 10µmol/L ranged from 24 to 36 h (mean = 32.4 h; SD: 5.8), for both oral and IV routes of administration (Figure 1).
the first 20 h. Osmotic diuresis was observed which led to moderately severe dehydration. with normal renal function was effective and safe. Jobard, et al. and haemodialysis in ethylene glycol poisoning.” Clinical Toxicology, 34(4), 373-377 (1996). Reported as S12 in the dossier Both patients intubated, ventilation; 30 yr old man given IV loading dose of 10 mg/kg 4MP, then haemodialysis started; between 4-6hr of dialysis, infusion of 2.5 mg/kg/h of 4MP given to compensate for loss of 4MP in dialysate. The 50yr old man given 4MP loading dose of 20mg/kg, one hr later haemodialysis started and maintenance dose of 4MP 1.5mg/kg/h infused during haemodialysis. The 30 yr old man recovered from coma in 48 h, anuria and haemodialysis given for 8 days; hospital stay of 14 days and complete recovery observed. The 50yr old man had flat EEG and QRS complexes with severe acidosis, anuria on admission, despite symptomatic treatment- he had haemodynamic instability and died 48hr after admission due to multiorgan failure and disseminated intravascular coagulation. Data from these 2 patients suggested that in cases of severe EG poisoning with toxic plasma EG levels and renal failure, a 4MP loading dose of followed by continuous infusion of 1 to 1.5mg/kg/h during the hrs of may be effective. Secondary pharmacodynamic effects Not evaluated. Time course of pharmacodynamic effects In the study reported by McMartin, 2012 (in healthy subjects, the time above the presumed minimum effective concentration of 10µmol/L ranged from 24 to 36 h (mean = 32.4 h; SD: 5.8), for both oral and IV routes of administration (Figure 1). Methylpyrazole
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