FOMEPIZOLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FOMEPIZOLE (FOMEPIZOLE).
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.
| Metabolism | Fomepizole is metabolized in the liver via cytochrome P450 enzymes, primarily CYP2E1, to 4-carboxypyrazole and other metabolites. |
| Excretion | Renal: 70-90% as unchanged drug and metabolites (4-carboxypyrazole, 4-hydroxymethylpyrazole); biliary/fecal: minor (<5% total). |
| Half-life | 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. |
| Protein binding | 5-15%; primarily to albumin. |
| Volume of Distribution | 0.6-0.8 L/kg; consistent with total body water distribution. |
| Bioavailability | Oral: 100% (complete absorption); IV: 100%. |
| Onset of Action | IV: 1-2 hours to achieve therapeutic plasma levels (10-20 μmol/L) for alcohol dehydrogenase inhibition. |
| Duration of Action | Therapeutic inhibition of alcohol dehydrogenase: 24-36 hours based on dosing interval (q12h for 48h, then q12h extended); serum concentrations maintained above 10 μmol/L. |
| Molecular Weight | 96.1 |
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.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; however, fomepizole is dialyzable. During hemodialysis, the dosing interval should be adjusted to every 4 hours or the dose increased to 1-1.5 mg/kg/h by continuous infusion. |
| Liver impairment | No specific dose adjustment for Child-Pugh class; use with caution in severe hepatic impairment due to limited data. |
| Pediatric use | 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; otherwise 10 mg/kg every 12 hours until ethylene glycol or methanol levels <20 mg/dL. |
| Geriatric use | No specific dose adjustment; use standard adult dosing with careful monitoring for adverse effects due to potential age-related decline in organ function. |
| 1st trimester | Limited human data; animal studies show fetal toxicity at high doses. Use only if potential benefit outweighs risk. |
| 2nd trimester | Same as T1; avoid unless necessary for ethylene glycol or methanol poisoning. |
| 3rd trimester | Same as T1; consider risk of maternal poisoning versus fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for FOMEPIZOLE (FOMEPIZOLE).
| Placental transfer | Crosses placenta in animals; human data limited but likely transfers due to low molecular weight and water solubility. |
| Breastfeeding | Not known if excreted in breast milk; due to indication for acute poisoning, breastfeeding unlikely during treatment. Consider pump and discard. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warnings.
| Serious Effects |
Hypersensitivity to fomepizole or any component of the formulation
| Precautions | Hypersensitivity reactions including urticaria, eosinophilia, and anaphylaxis have been reported., Dose adjustment may be required in patients with hepatic impairment., May cause dizziness, headache, and nausea., Monitor hepatic function and renal function during therapy., Use with caution in patients with a history of allergic reactions to pyrazole compounds. |
| Food/Dietary | No specific food interactions, but avoid alcohol. Maintain adequate hydration. Do not consume ethylene glycol or methanol (e.g., in adulterated beverages). |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | No adequate human studies; animal studies not reported. Use only if benefit outweighs risk. First trimester: unknown risk; second/third trimester: unknown risk. |
| Fetal Monitoring | Monitor liver function, renal function, acid-base status; fetal monitoring not specifically required. |
| Fertility Effects | No reported effects on fertility. |
| Clinical Pearls |
| Fomepizole is a competitive inhibitor of alcohol dehydrogenase used for ethylene glycol or methanol poisoning. Administer intravenously; loading dose 15 mg/kg, then 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol or methanol levels are <20 mg/dL and patient asymptomatic. Monitor for infusion site reactions, headache, nausea. Correct metabolic acidosis and maintain urine output. Hemodialysis indicated for severe acidosis, renal failure, or high levels. Fomepizole is preferred over ethanol due to better tolerability and no intoxication. |
| Patient Advice | Take fomepizole exactly as prescribed; it is given intravenously in the hospital. · Report any symptoms such as headache, nausea, dizziness, or pain at the injection site. · Do not consume alcohol while on fomepizole; alcohol may reduce its effectiveness and increase side effects. · Fomepizole treats poisoning from antifreeze or methanol; follow all medical advice for recovery. · Kidney function and blood levels of the poison will be monitored closely. |