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For many years, the only pharmacologic treatment for ethylene
glycol toxicity was ethanol, given by continuous intravenous infusion. Although
effective for this indication, there has been some concern that ethanol’s side
effect profile is not acceptable. The formulary at UK Hospital now includes a
new antidote for ethylene glycol toxicity, fomepizole (Antizol®
). Fomepizole, also known as 4-methylpyrazole (4-MP), is a competitive inhibitor
of alcohol dehydrogenase, with an affinity for the enzyme 8,000 times that of
ethanol. Alcohol dehydrogenase catalyzes the metabolism of ethylene glycol to
glycoaldehyde, which is then oxidized to produce glycolate, glycoxylate and
oxalate. The metabolic acidosis and renal tubular damage associated with
ethylene glycol toxicosis are caused primarily by glycolate and oxalate.
Fomepizole is effective in preventing the formation of toxic
metabolites that are responsible for the metabolic and renal complications of
ethylene glycol poisoning. It appears to be most useful in patients who present
soon after intoxication and who have not yet developed complications of
ingestion. Like ethanol, fomepizole may also be effective in the treatment of
methanol poisoning. Unfortunately, studies comparing the efficacy of fomepizole
and ethanol in these poisonings have not been conducted to date.
The cost of fomepizole is considerably higher than that of
ethanol. This difference in cost is magnified in patients with severe toxicity
requiring hemodialysis, as fomepizole needs to be dosed every four rather than
every 12 hours during dialysis. Unlike ethanol, fomepizole is not commonly
associated with adverse effects such as CNS depression, hypoglycemia,
hypothermia and agitation. Treatment with fomepizole may reduce costs if
patients can be admitted to floor beds rather than the intensive care unit while
receiving the antidote. However, patients with severe ethylene glycol poisoning
may require a unit bed because of complications associated with their condition.
The dosing regimen of fomepizole does not require the frequent monitoring and
subsequent adjustment of therapy that are necessary with ethanol therapy.
However, ethylene glycol levels as well as other intensive monitoring are still
necessary.
For these reasons, fomepizole has been added to the UKH
formulary with use restricted to Emergency Department and Pulmonary attending
physicians for use according to the following guidelines.
Guidelines for the Management of Ethylene Glycol Poisoning
Severe Intoxication
Diagnosis (one of the following):
Ethylene glycol > 50 mg/dL, with or without acidosis
Severe metabolic acidosis, with pH < 7.15
Renal failure, with serum creatinine > 3 mg/dL
Progression from moderate toxicity despite treatment with fomepizole or
ethanol
Treatment:
- Bolus dose of ethanol 7.6 – 10 mL/kg IV of 10% ethanol (v/v) in D5W over
30 minutes
- Place patient on hemodialysis
- Ethanol infusion or addition of ethanol to dialysate, titrated to a level
of 100 mg/dL
- Discontinue fomepizole and begin ethanol immediately upon beginning
dialysis.
Moderate Intoxication
Diagnosis (one of the following):
- Ethylene glycol 20 - 50 mg/dL, with or without acidosis
- Metabolic acidosis, with pH 7.15 – 7.35
- Moderate renal toxicity, with serum creatinine 1.5 - 3 mg/dL
- Progression from minor toxicity despite supportive measures
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Table 1. Ethanol Contraindications |
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Recovering alcoholic
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History of seizures
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Requiring close monitoring of CNS function
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Concurrent use of disulfiram (Antabuse®) or
metronidazole (Flagyl®)
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Patient who is abstinent for religious reasons
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Treatment:
Bolus dose of ethanol 7.6 – 10 mL/kg IV of 10% ethanol (v/v) in D5W over
30 minutes
Ethanol infusion, titrated to a level of 100 mg/dL until ethylene glycol
< 20 mg/dL
If ethanol is contraindicated (see Table 1),
- Bolus dose of fomepizole 15 mg/kg over 30 minutes
- Fomepizole 10 mg/kg every 12 hours for 4 doses
- Fomepizole 15 mg/kg every 12 hours until ethylene glycol < 20 mg/dL
Minor Intoxication
Diagnosis (all of the following):
Ethylene glycol < 20 mg/dL
pH 7.35 – 7.45
Normal renal function (serum creatinine < 1.5 mg/dL)
Treatment:
- Observation of patient for progression
- Supportive measures for toxicity-related symptoms
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_________________________________________________________________________________________________________
Approved by P&T
Committee: 11/99
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Posted on: 8/02
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For Internal University of Kentucky Chandler Medical Center Use Only
Comments to
Kelly Smith, Pharm.D.,
Last Modified:
August 13, 2006
Copyright © 2002, University of Kentucky Chandler Medical Center
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