Comparative Pharmacology
Head-to-head clinical analysis: FOMEPIZOLE versus FUSILEV.
Peer-Reviewed Evidence
Head-to-head clinical analysis: FOMEPIZOLE versus FUSILEV.
FOMEPIZOLE vs FUSILEV
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the first step in the metabolism of ethylene glycol and methanol to their toxic metabolites. By inhibiting alcohol dehydrogenase, fomepizole prevents the formation of toxic metabolites such as glycolic acid, glyoxylic acid, and oxalic acid from ethylene glycol, and formic acid from methanol.
FUSILEV (levoleucovorin) is the pharmacologically active isomer of folinic acid. It bypasses dihydrofolate reductase inhibition by dihydrofolate reductase inhibitors (e.g., methotrexate), providing reduced folate that is used in DNA synthesis and repair. It also enhances the efficacy of fluorouracil by stabilizing the ternary complex of thymidylate synthase, thereby inhibiting DNA synthesis.
Loading dose of 15 mg/kg intravenously over 15 minutes, followed by 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours if ethanol co-ingestion is present; otherwise 10 mg/kg every 12 hours until ethylene glycol or methanol levels <20 mg/dL.
Leucovorin (Fusilev) 200 mg/m2 IV over 2 hours, followed by 5-fluorouracil bolus and infusion, repeated every 2 weeks in combination regimens for advanced colorectal cancer.
None Documented
Clinical Note
moderateFomepizole + Artesunate
"The serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Fomepizole resulting in a loss in efficacy."
None Documented
Terminal: 5-7 hours in healthy adults; prolonged to 8-14 hours in patients with ethanol co-ingestion due to competitive inhibition; no significant change in severe renal impairment.
The terminal elimination half-life of the active metabolite, 5-methyltetrahydrofolate (5-MTHF), is approximately 6-8 hours in healthy adults; clinically, this supports twice-daily or daily dosing schedules.
Renal: 70-90% as unchanged drug and metabolites (4-carboxypyrazole, 4-hydroxymethylpyrazole); biliary/fecal: minor (<5% total).
Primarily hepatic metabolism; renal excretion of metabolites accounts for approximately 40-60% of the dose; fecal excretion is negligible.
Category C
Category C
Antidote
Antidote