Comparative Pharmacology
Head-to-head clinical analysis: FOMEPIZOLE versus PROTOPAM CHLORIDE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: FOMEPIZOLE versus PROTOPAM CHLORIDE.
FOMEPIZOLE vs PROTOPAM CHLORIDE
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.
Reactivates acetylcholinesterase inhibited by organophosphate poisoning by binding to the organophosphate moiety, forming a complex that undergoes hydrolysis to regenerate active enzyme. Also has a direct neutralization effect on certain organophosphates.
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.
1-2 g IV over 15-30 minutes, may repeat after 1 hour if muscle weakness persists, then every 3-8 hours as needed for 24-48 hours.
None Documented
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."
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.
Terminal elimination half-life is approximately 1.7 hours in adults. In renal impairment, half-life may be prolonged up to 6 hours, requiring dose adjustment.
Renal: 70-90% as unchanged drug and metabolites (4-carboxypyrazole, 4-hydroxymethylpyrazole); biliary/fecal: minor (<5% total).
Renal excretion is the primary route, with 80-90% of a dose eliminated unchanged in urine within 30 minutes; the remainder is metabolized and excreted fecally.
Category C
Category C
Antidote
Antidote