However, new data reveals that fomepizole may be hepatoprotective in high dose acetaminophen toxicity when reviewed in animal models, and possibly an effective adjunct to treatment regimens, especially in massive overdose or in unknown time of ingestion (TOI). N-acetylcysteine (NAC) is the only Food and Drug Administration (FDA) approved antidote in acetaminophen toxicity and is the mainstay treatment for significant acute overdose. Glutathione depletion leads to more NAPQI and resultant hepatic necrosis. Glutathione stores become depleted in large acetaminophen overdoses and are subsequently unable to reduce all the generated NAPQI to its nontoxic metabolites. As shifts toward the CYP2E1 pathway occur, glutathione serves to reduce NAPQI to nontoxic metabolites.

However, in large overdoses these pathways become saturated, and more acetaminophen is converted by CYP2E1 into the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Acetaminophen is metabolized by glucuronidation primarily to nontoxic metabolites. Toxicity develops at 150 mg/kg or >7.5 g/day.

However, acetaminophen is thought to inhibit COX receptors in the CNS selectively. The therapeutic antipyretic mechanism of action is not well understood.

2 According to the United States Acute Liver Failure Study Group registry, 42% of all cases of acute liver failure in the United States are attributable to acetaminophen overdose. 1 Each year in the United States, acetaminophen overdoses are estimated to result in 56,000 emergency department visits, 2,600 hospital admissions, and 500 deaths. Acetaminophen toxicity is one of the most common causes of liver toxicity in the United States.Īcetaminophen ingestions are the most common cases called into poison centers in the United States, accounting for more than 100,000 calls per year.

Paracetamol antidote