Question of the Week
What do you do when fomepizole is not available?
Many hospitals do not stock fomepizole because of cost and because they infrequently have patients with toxic alcohol poisoning. Fomepizole is an inhibitor of alcohol dehydrogenase, the enzyme that starts the metabolic breakdown of toxic alcohols to their toxic metabolites. Metabolism of ethylene glycol results in production of glyoxylic acid and oxalic acid. These organic acids produce metabolic acidosis and eventual renal toxicity. Formic acid is the organic acid produced by metabolism of methanol. Formic acid contributes to the acidosis and causes blindness.
One option for a hospital that doesn’t have fomepizole is to have a pre-existing arrangement with neighboring/sister/system hospital(s) for the sharing of fomepizole stocks. When a patient presents with a likely ingestion of one of the toxic alcohols, a call is placed to the neighboring/sister/system hospital and fomepizole is transferred to the hospital in need or the patient is transferred immediately to the hospital with adequate fomepizole stock. Once a loading dose of fomepizole is administered (15 mg/kg IV) the enzyme is blocked for 12 hours. Further metabolism of the toxic alcohol does not occur and sufficient time is gained in which to determine treatment/transfer options. Maintenance dosage is 10 mg/kg every 12 hours.
Another option is to administer the “older” antidote, ethanol. If this option is chosen a hospital should have a protocol in place with pharmacy as to the emergent preparation and administration of ethanol. It is preferably administered intravenously but may also be administered orally. Ethanol is a competitive substrate of the same enzyme, alcohol dehydrogenase, when blood alcohol levels are in the range of 100-150 mg/dL. A loading dose of 0.8 g/kg of 10% ethanol solution is given to the patient followed by a maintenance drip of 0.1-0.15 g/kg/hour of 10% ethanol. Hourly blood alcohol levels must be checked to make sure the ethanol concentration remains therapeutic. If the patient is a chronic alcoholic, then the maintenance dose needs to be doubled.
Note that any metabolites already formed will not be blocked by fomepizole or ethanol, and appropriate care still needs to be instituted. If you have any further questions please don’t hesitate to contact us via the Tennessee Poison Center at 1-800-222-1222.
Question prepared by: John Benitez, MD, MPH Medical Toxicologist