Biomaterial Database

Fomepizole dosing during continuous renal replacement therapy - an observational study. 2022

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

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. CONCLUSIONS 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.

UI	MeSH Term	Description	Entries
D006435	Renal Dialysis	Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION.	Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077604	Fomepizole	A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL.	4-Methylpyrazole,4-Methylpyrazole Monohydrochloride,Antizol,4 Methylpyrazole,4 Methylpyrazole Monohydrochloride
D000079664	Continuous Renal Replacement Therapy	Procedures with continuous blood purification (e.g., dialysis, filtration or perfusion) via vascular access designed to mimic kidney function in kidney diseases (e.g., ACUTE RENAL FAILURE and poisoning).	CAVHD,CRRT Technique,CVVH Technique,CVVHD,CVVHDF,Continuous Arterio-Venous Ultrafiltration,Continuous RRT,Continuous Renal Replacement Procedure,Continuous Veno-Venous Hemodiafiltration,Continuous Veno-Venous Hemodialysis,Continuous Veno-Venous Hemofiltration,Continuous Venovenous Hemodiafiltration,Continuous Venovenous Hemodialysis,Continuous Venovenous Hemofiltration,Hemofiltration, Continuous Arteriovenous,SCUF Technique,Slow Continuous Ultrafiltration,Arterio-Venous Ultrafiltration, Continuous,Arteriovenous Hemofiltration, Continuous,CVVH Techniques,Continuous Arterio Venous Ultrafiltration,Continuous Arterio-Venous Ultrafiltrations,Continuous Arteriovenous Hemofiltration,Continuous Arteriovenous Hemofiltrations,Continuous RRTs,Continuous Veno Venous Hemodiafiltration,Continuous Veno Venous Hemodialysis,Continuous Veno Venous Hemofiltration,Continuous Veno-Venous Hemodiafiltrations,Continuous Veno-Venous Hemodialyses,Continuous Veno-Venous Hemofiltrations,Continuous Venovenous Hemodiafiltrations,Continuous Venovenous Hemodialyses,Continuous Venovenous Hemofiltrations,Hemodiafiltration, Continuous Veno-Venous,Hemodiafiltration, Continuous Venovenous,Hemodialysis, Continuous Veno-Venous,Hemodialysis, Continuous Venovenous,Hemofiltration, Continuous Veno-Venous,Hemofiltration, Continuous Venovenous,RRT, Continuous,SCUF Techniques,Slow Continuous Ultrafiltrations,Ultrafiltration, Continuous Arterio-Venous,Veno-Venous Hemodiafiltration, Continuous,Veno-Venous Hemodialyses, Continuous,Veno-Venous Hemodialysis, Continuous,Veno-Venous Hemofiltration, Continuous,Venovenous Hemodiafiltration, Continuous,Venovenous Hemodialysis, Continuous,Venovenous Hemofiltration, Continuous
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000432	Methanol	A colorless, flammable liquid used in the manufacture of FORMALDEHYDE and ACETIC ACID, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness.	Alcohol, Methyl,Carbinol,Sodium Methoxide,Wood Alcohol,Alcohol, Wood,Methoxide, Sodium,Methyl Alcohol
D000931	Antidotes	Agents counteracting or neutralizing the action of POISONS.	Antidote,Theriacs
D017582	Renal Replacement Therapy	Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys.	Kidney Replacement Therapy,Replacement Therapy, Kidney,Replacement Therapy, Renal,Therapy, Kidney Replacement,Therapy, Renal Replacement,Kidney Replacement Therapies,Renal Replacement Therapies,Replacement Therapies, Kidney,Replacement Therapies, Renal,Therapies, Kidney Replacement,Therapies, Renal Replacement