emDOCs / ToxCard - February 1st, 2023 - By Morgan Penzler; Kathryn T Kopec
Reviewed by: James Dazhe Cao; Alex Koyfman; Brit Long
Indications for Fomepizole Treatment in APAP Toxicity:
Currently, fomepizole has only been used experimentally in patients who are at a high risk of developing significant hepatotoxicity. One method of determining risk of severe hepatotoxicity is using the aminotransferase multiplication product. An aminotransferase multiplication product of > 10,000 mg/L x IU/L has been associated with a high likelihood of developing hepatotoxicity. This level is obtained by multiplying the serum APAP concentration by the alanine transaminase activity (ALT) level. Other markers that may indicate patients that are at high risk for subsequent development of significant hepatotoxicity include a history of chronic ethanol use (as these patients have upregulated CYP2E1), delay in administration of NAC > 8 hours after ingestion, or a serum APAP half-life of > 4 hours.It has also been suggested that in massive overdoses, APAP levels of > 600 mcg/mL the use of fomepizole may be beneficial.
Dosing of fomepizole is not yet standardized in its use for APAP toxicity. In one study, the standard dosing for toxic alcohol ingestion was used (15 mg/kg IV over 30 min, with repeated doses of 10 mg/kg every 12 hours) at the physicians’ discretion or until APAP levels were undetectable.7,16 Other case reports have noted using a single dose of 15 mg/kg IV.