Newsletters

POSTED: October 30th, 2020
POSTED IN: EM Pulse - The Official Newsletter of MOCEP, September/October 2020,

Written by Evan Schwarz, MD, FACEP, FACMT

Most emergency physicians are familiar with fomepizole as we use it to treat patients following toxic exposures to methanol or ethylene glycol. Well did you know it may be useful for something else?

It’s still very early, but fomepizole may be useful as an adjunctive treatment for acetaminophen toxicity. To be clear, these patients still need NAC and should still receive NAC. However, there may be times with after consulting with a toxicologist or poison center, that they ask you to administer fomepizole as well.

You may ask, but why? Doesn’t fomepizole block alcohol dehydrogenase and isn’t that how it treats toxic alcohol exposures? Well, yes, but that’s not all it does. Fomepizole also blocks CYP450 2E1, the enzyme that metabolizes acetaminophen to all the toxic metabolites that do the damage. Additionally, it acts at the mitochondria to assist with acetaminophen-induced mitochondrial dysfunction. Again while we understand these mechanisms and it is plausible that fomepizole could be useful, we still aren’t sure it is really needed. Of course outside of cost, there is little downside to administering it.

So, who might we consider treating with fomepizole? Well, it’s difficult to say. There is some basic science data, but there are no randomized or really any observational trials to assist with this. Mainly, human evidence is based on case reports and case series where the treating physicians were worried that NAC, by itself, wasn’t going to be enough. Some potentially beneficial situations may be in patients with really elevated acetaminophen concentrations.  A case report presented at a recent toxicology meeting discussed a patient with an initial acetaminophen concentration of 1141 micrograms/ml treated with fomepizole. A few other cases were also reported with patients presenting with levels generally well above 300 micrograms/ml. Additionally, there were also reports of patients with significant acidosis (thought to be from mitochondrial dysfunction) with only slightly elevated levels receiving fomepizole.

Of course, maybe all of these patients would have done okay without fomepizole and all did receive NAC. Additionally if the patients didn’t do well, their cases likely weren’t reported published. All this to say that the patient should still receive NAC if the patient meets criteria, but if the toxicologist or poison center also asks for fomepizole, it might not be an accident!