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Fomepizole dosing during continuous renal replacement therapy - an observational study
Yvonne E Lao1, Trond Vartdal2, Sten Froeyshov3
1Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.
Clinical Toxicology (Philadelphia, Pa.)
|September 29, 2021
Summary
Reduced fomepizole doses during continuous renal replacement therapy (CRRT) maintain effective plasma concentrations for poisoning treatment. This study confirms the safety and efficacy of halved maintenance doses in patients undergoing CRRT.
Area of Science:
- Toxicology
- Pharmacokinetics
- Nephrology
Background:
- Fomepizole is a crucial antidote for methanol and ethylene glycol poisoning.
- High cost and limited availability of fomepizole pose challenges, especially during mass poisonings.
- Previous pharmacokinetic data suggested a 50% reduced maintenance dose for fomepizole during CRRT.
Purpose of the Study:
- To evaluate if the reduced fomepizole maintenance dose during CRRT achieves plasma concentrations above the therapeutic threshold of 10 µmol/L.
- To investigate the elimination kinetics of fomepizole during CRRT, a previously unstudied area.
Main Methods:
- Prospective observational study involving adult patients receiving fomepizole and CRRT.
- Collection of plasma samples (pre-filter) and dialysate for fomepizole concentration measurements.
- High-performance liquid chromatography (HPLC) used for precise fomepizole quantification.
Main Results:
- Ninety-eight percent of plasma samples maintained concentrations above the minimum 10 µmol/L threshold.
- Fomepizole elimination was observed during CRRT, with a median saturation/sieving coefficient of 0.85.
- The dialysis clearance of fomepizole was measured at 28 mL/min.
Conclusions:
- Fomepizole is effectively eliminated during CRRT.
- The revised dosing recommendations for fomepizole in CRRT patients are safe, maintaining therapeutic plasma levels.
- The maintenance dose of fomepizole during CRRT can be safely halved compared to intermittent hemodialysis.
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