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Fomepizole dosing during continuous renal replacement therapy - an observational study.

Authors:
Yvonne E Lao Trond Vartdal Sten Froeyshov Brian Latimer Christiane Kvaerner Marija Mataric Peter Holm Siri Foreid Dag Jacobsen Kenneth McMartin Knut Erik Hovda

Clin Toxicol (Phila) 2022 Apr 29;60(4):451-457. Epub 2021 Sep 29.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Background: Fomepizole is the preferred antidote for treatment of methanol and ethylene glycol poisoning, acting by inhibiting the formation of the toxic metabolites. Although very effective, the price is high and the availability is limited. Its availability is further challenged in situations with mass poisonings. Therefore, a 50% reduced maintenance dose for fomepizole during continuous renal replacement therapy (CRRT) was suggested in 2016, based on pharmacokinetic data only. Our aim was to study whether this new dosing for fomepizole during CRRT gave plasma concentrations above the required 10 µmol/L. Secondly, we wanted to study the elimination kinetics of fomepizole during CRRT, which has never been studied before.

Methods: Prospective observational study of adult patients treated with fomepizole and CRRT. We collected samples from arterial line (pre-filter) = plasma concentration, post-filter and dialysate for fomepizole measurements. Fomepizole was measured using high-pressure liquid chromatography with a reverse phase column.

Results: Ten patients were included in the study. Seven were treated with continuous veno-venous hemodialysis (CVVHD) and three with continuous veno-venous hemodiafiltration (CVVHDF). Ninety-eight percent of the plasma samples were above the minimum plasma concentration of 10 µmol/L. Fomepizole was removed during CRRT with a median saturation/sieving coefficient of 0.85 and dialysis clearance of 28 mL/min.

Conclusion: Fomepizole was eliminated during CCRT. The new dosing recommendations for fomepizole and CRRT appeared safe, by maintaining the plasma concentration above the minimum value of 10 µmol/L. Based on these data, the fomepizole maintenance dose during CRRT could be reduced to half as compared to intermittent hemodialysis.

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http://dx.doi.org/10.1080/15563650.2021.1980581DOI Listing
April 2022

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Fomepizole dosing during continuous renal replacement therapy - an observational study.

Authors:
Yvonne E Lao Trond Vartdal Sten Froeyshov Brian Latimer Christiane Kvaerner Marija Mataric Peter Holm Siri Foreid Dag Jacobsen Kenneth McMartin Knut Erik Hovda

Clin Toxicol (Phila) 2022 Apr 29;60(4):451-457. Epub 2021 Sep 29.

Norwegian National Unit for CBRNE Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Background: Fomepizole is the preferred antidote for treatment of methanol and ethylene glycol poisoning, acting by inhibiting the formation of the toxic metabolites. Although very effective, the price is high and the availability is limited. Its availability is further challenged in situations with mass poisonings. Read More

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Authors:
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Toxicol Rep 2021 6;8:804-807. Epub 2021 Apr 6.

Department of Medicine, Western University, London, ON, Canada.

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Cost-effectiveness of hospital treatment and outcomes of acute methanol poisoning during the Czech Republic mass poisoning outbreak.

Authors:
Jan Rulisek Martin Balik Ferdinand Polak Petr Waldauf Daniela Pelclova Jan Belohlavek Sergey Zakharov

J Crit Care 2017 06 6;39:190-198. Epub 2017 Mar 6.

Department of Occupational Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Toxicological Information Centre, Na Bojisti 1, 120 00 Prague 2, Czech Republic. Electronic address:

Purpose: During an outbreak of mass methanol poisoning in the Czech Republic in 2012-2014, we compared the total hospital costs and one-year medical costs in the patients treated with different antidotes (fomepizole versus ethanol) and modalities of hemodialysis (intermittent hemodialysis, IHD, versus continuous renal replacement therapy, CRRT).

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