EthyleneGlycolandMethanolPoisoningTreatment

Formanyyears,theonlypharmacologictreatmentforethyleneglycolormethanoltoxicitywasethanol,giveneitherorallyorbycontinuous
intravenousinfusion.1Althougheffectivefortheseindications,concernexistsregardingethanolsharmfulsideeffectprofile.Theformularyat
UKHospitalincludesanotherantidoteforethyleneglycoltoxicity,fomepizole(Antizol),whichisalsoFDAapprovedformethanolpoisonings.
Fomepizoleisacompetitiveinhibitorofalcoholdehydrogenase,withanaffinityfortheenzyme8,000timesthatofethanol.2Alcohol
dehydrogenasecatalyzesthemetabolismofethyleneglycoltoglycoaldehyde,whichisthenoxidizedtoproduceglycolicacid,glycoxylicacid,and
oxalicacid.Themetabolicacidosisandrenaltubulardamageassociatedwithethyleneglycolingestionarecausedprimarilybyglycolicandoxalic
acidsrespectively.3,4Alcoholdehydrogenasealsocatalyzestheconversionofmethanoltoformaldehydewithsubsequentoxidationtoformic
acid,resultingintheoculardamageandblindnessassociatedwiththismetabolite.1,5

Fomepizoleiseffectiveinpreventingtheformationoftoxicmetabolitesthatareresponsibleforthecomplicationsofethyleneglycoland
methanolpoisoning.Itappearstobemostusefulinpatientswhopresentsoonafterintoxicationandwhohavenotyetdevelopedcomplications
ofingestion.Largelyduetothelowincidenceofmethanolandethyleneglycoltoxicities,comparisonstudiesbetweenethanolandfomepizole
arecurrentlynotavailable.Themaindisadvantageoffomepizoleoverethanolistheacquisitioncost.Thisdifferenceincostismagnifiedin
patientswithseveretoxicityrequiringhemodialysis,duringwhichfomepizoleneedstobedosedeveryfourratherthanevery12hours.Unlike
ethanol,fomepizoleisnotcommonlyassociatedwithadverseeffectssuchasCNSdepression,hypoglycemia,hypothermiaandagitation.
Treatmentwithfomepizolemayreducecostsifpatientscanbeadmittedtoacutecareareasratherthantheintensivecareunitwhilereceiving
theantidote.Thedosingregimenoffomepizoledoesnotrequirethefrequentmonitoringandsubsequentadjustmentoftherapythatare
necessarywithethanoltreatment.Otherlaboratorymonitoring,suchasethyleneglycolandmethanolserumconcentrations,arestill
necessary.1,3

Forthesereasons,fomepizolesindicationforuseatUKHhasbeenexpandedtoincludebothethyleneglycolandmethanoltoxicity.Inaddition,
therearenolongerUKHformularyrestrictionsforuseaccordingtothefollowingguidelines.

DeannaMcMahon,KyleWeant,ShaneWinstead;6/2009
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GuidelinesfortheManagementofEthyleneGlycol(EG)andMethanol
Poisoning

IfhemodialysisNOTindicatedperrenalconsult,followmoderateintoxicationtreatmentalgorithm
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Fomepizoledosinginhemodialysis
DOSEATTHEBEGINNINGOFHEMODIALYSIS
If<6hourssincelastfomepizoledose

Donotadministernextscheduleddose.

If6hourssincelastfomepizoledose

Administernextscheduleddose.

DOSEDURINGHEMODIALYSIS
Administerdoseevery4hours.
DOSEATTHECOMPLETIONOFHEMODIALYSIS
Timebetweenlastdoseandendofhemodialysis

Doseadministeredatendofhemodialysissession

<1hour

Donotadministerdoseatendofhemodialysis.

13hours

Administer50%ofnextscheduleddose.

>3hours

Administernextscheduleddose.

MAINTENANCEDOSEAFTERHEMODIALYSIS
Givenextscheduleddose12hoursfromlastfomepizoledoseifindicated.

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IffomepizoleisindicatedBUTthereishistoryofhypersensitivitytofomepizole,ethanolshouldbeusedperthefollowingguidelines(table2).
Ethanolshouldbetitratedtoalevelof100mg/dLuntilethyleneglycolormethanollevelsarebelow20mg/dL(seetable3forethanol
contraindications).
Table2.TherapeuticDosesofEthanolBasedonPatientsDrinkingHistory

AbsoluteEthanolDose

Volumeof10%IVEthanolSolution

Loadingdose

600700mg/kg

7.610mL/kginD5Wover30minutes

Maintenancedose

66mg/kg/hr

0.83mL/kg/hr

Maintenancedoseduringhemodialysis

169mg/kg/hr

2.13mL/kg/hr

Maintenancedose

154mg/kg/hr

1.96mL/kg/hr

Maintenancedoseduringhemodialysis

257mg/kg/hr

3.26mL/kg/hr

Nondrinker

Chronicdrinker

Table3.EthanolContraindications
Recoveringalcoholic
Historyofseizures
RequiringclosemonitoringofCNSfunction
Concurrentuseofdisulfiram(Antabuse)ormetronidazole(Flagyl)
Patientwhoisabstinentforreligiousreasons

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References:

1.
BarcelouxDG,BondGR,KrenzelokEP,CooperH,ValeJA.AmericanAcademyofClinicalToxicologypracticeguidelinesonthetreatment
ofmethanolpoisoning.JToxicolClinToxicol2002;40:41546.
2.
Antizol[packageinsert].In.PaloAlto,CA:JazzPharmaceuticals,Inc;2006.
3.
BarcelouxDG,KrenzelokEP,OlsonK,WatsonW.AmericanAcademyofClinicalToxicologyPracticeGuidelinesontheTreatmentof
EthyleneGlycolPoisoning.AdHocCommittee.JToxicolClinToxicol1999;37:53760.
4.
BrentJ,McMartinK,PhillipsS,etal.Fomepizoleforthetreatmentofethyleneglycolpoisoning.MethylpyrazoleforToxicAlcoholsStudy
Group.NEnglJMed1999;340:8328.
5.
BrentJ,McMartinK,PhillipsS,AaronC,KuligK.Fomepizoleforthetreatmentofmethanolpoisoning.NEnglJMed2001;344:4249.

DeannaMcMahon,KyleWeant,ShaneWinstead;6/2009
Approved by P&T Committee: 5/2009 | Posted on: 8/31/09 | For Internal University of Kentucky Healthcare Use Only

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