Bedside Snapshot
- Use It For
- Suspected or confirmed ethylene glycol or methanol poisoning; adjunct to hemodialysis; toxicologist-directed use in diethylene glycol or massive acetaminophen ingestion (off-label)
- Adult Dose
- Toxic alcohol: 15 mg/kg IV over 30 min, then 10 mg/kg every 12 hr ×4, then 15 mg/kg every 12 hr (no fixed max)
- Hemodialysis: every 4 hr, with start- and end-of-run timing rules (see Dosing); every 12 hr after dialysis
- Pediatric Dose
- Same mg/kg regimen as adults: 15 mg/kg IV load, then 10 mg/kg every 12 hr ×4, then 15 mg/kg every 12 hr; every 4 hr on hemodialysis (not FDA-established; neonates: toxicologist only)
- Onset / Duration
- IV: therapeutic level expected by the end of the 30-min loading infusion / dosed every 12 hr (every 4 hr during hemodialysis); the label gives no measured duration
- Do Not Give / Hold If
- Serious hypersensitivity to fomepizole or other pyrazoles (use ethanol); never undiluted or IV push
- Watch For
- Rising anion gap or falling pH (metabolites formed: dialysis); new vision loss (methanol); AKI or low Ca²⁺ (ethylene glycol); rash, eosinophilia, rising AST/ALT
- Reversal / Rescue
- Hemodialysis per EXTRIP criteria (coma, seizures, vision loss, pH ≤7.15, anion gap >24, impaired kidney function); fallback IV ethanol. Differs from FDA label: label threshold is a level of 50 mg/dL or more.
- Must Remember
- Give it on suspicion, not on the level. Every 12 hr becomes every 4 hr on hemodialysis: a missed dose restarts toxic metabolism.
Indications
ED / ICU / Transport
- Ethylene glycol poisoning: confirmed ingestion (antifreeze, coolants, de-icers); FDA-labeled, alone or with hemodialysis
- Methanol poisoning: confirmed ingestion (windshield washer fluid, solvents, contaminated or counterfeit spirits); FDA-labeled
- Suspected toxic alcohol ingestion before levels return: start on suspicion from the history, an anion gap metabolic acidosis, a raised osmolar gap, visual disturbance or urinary oxalate crystals, or a measured ethylene glycol or methanol level >20 mg/dL (FDA-labeled)
- Adjunct to extracorporeal treatment: keeps alcohol dehydrogenase (ADH) blocked while hemodialysis or continuous renal replacement therapy (CRRT) removes the parent alcohol and acid metabolites
Other Uses
- Diethylene glycol and butoxyethanol (glycol ether) poisoning: ADH-dependent toxicity; case reports, including children (off-label, toxicologist-directed)
- Massive acetaminophen ingestion: some toxicologists add fomepizole to full-dose acetylcysteine in high-risk ingestions (the 2023 US/Canada consensus defines high risk as ≥30 g, or a level above the high-risk nomogram line that starts at 300 mcg/mL at 4 hr); it blocks CYP2E1 formation of the toxic metabolite NAPQI. That consensus found the data insufficient for a standard fomepizole recommendation and gives no fomepizole criteria (off-label, toxicologist only)
Dosing & Administration
Toxic alcohol doses follow the label's mg/kg regimen. Hemodialysis timing follows EXTRIP criteria (see Monitoring). This differs from the FDA label, whose dialysis threshold is a level of 50 mg/dL or more.
Available Forms
- Injection: 1 g/mL (1,000 mg/mL) in a 1.5 mL (1.5 g) single-dose glass vial, preservative-free; generic fomepizole injection (Antizol is the original brand). Must be diluted before use.
- Appearance: clear to yellow liquid that solidifies below 25°C (77°F). Solidifying does not touch efficacy, safety or stability. Liquefy it by holding the vial in your hand or running it under warm water.
Adult Dosing
| Indication | Dose & Route | Repeat / Max | Notes |
|---|---|---|---|
| Toxic alcohol (ethylene glycol, methanol): loading | 15 mg/kg IV loading dose, infused over 30 min | Single loading dose; weight-based, no fixed max | Start on suspicion; do not wait for levels. Dose on actual body weight. The label gives mg/kg doses without naming a dosing weight or a cap; for a patient over 100 kg confirm the dose with pharmacy or the poison center. |
| Toxic alcohol: maintenance (no dialysis) | 10 mg/kg IV every 12 hr for 4 doses, then 15 mg/kg IV every 12 hr | Continue until the level is <20 mg/dL or undetectable, the patient is asymptomatic and pH is normal | The step back up to 15 mg/kg (from the 6th dose, 60 hr after the load) offsets autoinduction, which speeds fomepizole clearance after 30–40 hr. |
| Starting intermittent hemodialysis | Last dose <6 hr ago: no dose. 6 hr or more: give the next scheduled dose | Then dose every 4 hr while on dialysis | Fomepizole is dialyzable; the 12-hr interval leaves ADH unblocked during a run. |
| During intermittent hemodialysis | Next scheduled dose (10 or 15 mg/kg) IV every 4 hr | Every 4 hr until dialysis stops | Keep the same mg/kg step of the schedule; only the interval changes. |
| End of intermittent hemodialysis | Last dose <1 hr ago: no dose. 1–3 hr: half the next scheduled dose. Over 3 hr: the next scheduled dose | Then the next dose 12 hr after the last one | Recheck the level and anion gap after dialysis: glycolate and toxic alcohol can rebound if ADH blockade lapses. |
| During CRRT | During CRRT use about half the intermittent-HD maintenance dose, per the Lao 2022 study; fomepizole is removed by CRRT. | Schedule per toxicology and pharmacy | Lao 2022 (10 patients): a maintenance dose 50% lower than intermittent hemodialysis kept 98% of plasma levels above 10 µmol/L. EXTRIP: fomepizole is extensively removed by ECTR, and the dose must be adjusted during the session or ADH inhibition can lapse. The exact schedule is not settled. |
| Massive acetaminophen ingestion (off-label) | Dose and duration per toxicologist | No standard regimen: toxicologist-directed | Never replaces acetylcysteine. Consensus: insufficient data for a standard recommendation; consult a poison center or toxicologist. |
Pediatric Dosing
| Indication | Dose (per kg) & Route | Max Single / Max Total | Notes |
|---|---|---|---|
| Toxic alcohol: loading | 15 mg/kg IV loading dose over 30 min | Weight-based, no fixed max; same mg/kg as adults | Label: safety and effectiveness not established in children. Published pediatric cases used the adult mg/kg regimen and tolerated it well. |
| Toxic alcohol: maintenance | 10 mg/kg IV every 12 hr for 4 doses, then 15 mg/kg IV every 12 hr | Same stop criteria as adults (level <20 mg/dL, asymptomatic, normal pH) | Use the adult hemodialysis schedule (every 4 hr on dialysis). Diluted volume is set by the minimum 100 mL in the label: confirm fluid limits with pharmacy in small children. |
| Neonates and young infants | Not established: toxicologist-directed (specialist use) | — | No published neonatal dosing data. Contact a poison center. |
Weight-based dose checks: pediatric weight-based dosing.
Preparation & Administration
- Syringe: draw up with a non-polycarbonate syringe and needle; fomepizole can damage polycarbonate.
- Dilution: add the dose to at least 100 mL of 0.9% sodium chloride or D5W.
- Infusion: infuse the whole bag over 30 min on a pump. Never give undiluted or as an IV push: bolus injection caused venous irritation and phlebosclerosis in volunteers.
- Stability: diluted solution is stable for at least 24 hr refrigerated or at room temperature; no preservative, so discard after 24 hr. Discard if hazy, discolored or precipitated.
- Timing: chart the clock time of every dose; the next dose depends on it, especially around dialysis.
Contraindications & Precautions
Contraindications
- Hypersensitivity: documented serious hypersensitivity to fomepizole or other pyrazoles. In confirmed toxic alcohol poisoning with such a history, use IV ethanol as the alternative ADH blocker under toxicology guidance.
Precautions
- Allergic reactions: Mild rash and eosinophilia have happened. Watch for hypersensitivity during every infusion.
- Repeated dosing: A transient transaminase rise and eosinophilia occur with repeated doses. Check liver enzymes and the white cell count.
- Ethanol on board: Ethanol and fomepizole slow each other’s elimination. Follow levels, and don't skip fomepizole.
- Late presentation: Fomepizole stops new toxic metabolites and nothing more. Acid that has already formed (formate, glycolate) means the acidemia needs correcting, and organ injury often needs extracorporeal treatment.
- Administration: Dilute in at least 100 mL. Never give it undiluted or as a bolus. Avoid polycarbonate syringes.
Hold / Reassess If
- Signs of an allergic reaction during an infusion: stop the infusion, reassess and treat per protocol
- Dialysis started or stopped: re-time the next dose by the hemodialysis rules, do not simply continue every 12 hr
- Level <20 mg/dL or undetectable, asymptomatic and normal pH: stop criteria met
Adverse Effects & Toxicity
Common
- Headache: 14%
- Nausea: 11%
- Dizziness, drowsiness, bad or metallic taste: 6% each
- Infusion-site pain, inflammation or phlebitis: about 3% or less. Bolus injections (5-min, 25 mg/mL) caused phlebosclerosis in 2 of 6 volunteers. Always dilute in at least 100 mL and infuse over 30 min
- Vomiting, diarrhea, vertigo, rash: about 3% or less
Serious / Life-Threatening
| Effect | Recognition | Management |
|---|---|---|
| Hypersensitivity | Mild rash and eosinophilia reported (label); serious hypersensitivity to any pyrazole is a contraindication | Stop the infusion; treat anaphylaxis per protocol if it occurs; switch to ethanol under toxicology guidance |
| Bradycardia, hypotension, seizure | About 3% or less in trials; hard to separate from the poisoning itself | Continuous ECG and BP; correct acidemia, Ca²⁺ and K⁺; treat seizures per protocol; consider extracorporeal treatment |
| Venous irritation, phlebosclerosis | Pain, redness or a cord along the vein; seen with bolus injection | Always dilute to at least 100 mL and infuse over 30 min; change the site |
| Transaminase rise, eosinophilia | Rising AST/ALT or eosinophil count with repeated doses | Usually transient; trend ALT and the white cell count |
Overdose & Toxicity Management
- Signs: In healthy volunteers given 50–100 mg/kg (3–6 times the usual dose), nausea, dizziness and vertigo appeared. In one subject they lasted up to 30 hr.
- Management: Supportive care. There is no antidote. Fomepizole is dialyzable, so hemodialysis may help.
- Treatment failure: A rising anion gap or worsening acidosis on fomepizole means metabolites have already formed or a dose was missed. Check dose times, correct acidemia and arrange extracorporeal treatment.
Monitoring
| Parameter | When / How Often | Target / Act If |
|---|---|---|
| Clinical: mental status, seizures | Continuous; frequent neuro checks while acidemic | Coma or seizures: extracorporeal treatment indicated (EXTRIP); protect the airway |
| Clinical: vision (methanol) | At presentation and with each assessment | New visual deficit: extracorporeal treatment indicated; continue folic or folinic acid |
| Clinical: ECG, BP, urine output | Continuous ECG; hourly urine output | Arrhythmia from acidosis, K⁺ or Ca²⁺ shifts: correct; falling urine output in ethylene glycol: suspect oxalate kidney injury |
| Laboratory: blood gas, anion gap, bicarbonate | Baseline, then serially until acid–base is normal, and after each dialysis run | pH or anion gap at EXTRIP thresholds (table below): extracorporeal treatment; rebound after dialysis: keep ADH blocked and recheck |
| Laboratory: osmolality, toxic alcohol levels | Baseline; repeat to guide stopping | Stop fomepizole when methanol or ethylene glycol is <20 mg/dL or undetectable, the patient is asymptomatic and pH is normal |
| Laboratory: creatinine, K⁺, calcium, glucose | Baseline, then serially | Rising creatinine (KDIGO stage 2–3 AKI) in ethylene glycol: dialysis; low ionized calcium suggests oxalate formation |
| Laboratory: ethanol level | Baseline | Co-ingested ethanol delays toxic metabolite formation and slows fomepizole clearance; still give fomepizole |
| Laboratory: AST/ALT, white cell count | Daily with repeated dosing | Transient rise or eosinophilia expected; marked rise: discuss with toxicology |
| Infusion safety: dose timing | Every dose and every dialysis start or stop | Use the hemodialysis timing rules; a missed dose during dialysis lets metabolism restart |
When to Add Extracorporeal Treatment (EXTRIP)
| Finding | Methanol | Ethylene Glycol |
|---|---|---|
| Clinical features | Coma, seizures, new vision deficit or impaired kidney function: ECTR recommended | Coma, seizures, or AKI KDIGO stage 2–3: ECTR recommended; CKD with eGFR <45: suggested |
| Acid–base | pH ≤7.15, anion gap >24 mmol/L, or acidosis persisting despite antidote and supportive care | Anion gap >27 mmol/L or glycolate >12 mmol/L: recommended; anion gap 23–27 mmol/L or glycolate 8–12 mmol/L: suggested (glycolate where available) |
| Level on fomepizole | Methanol >70 mg/dL (700 mg/L) | Ethylene glycol >310 mg/dL (50 mmol/L) or osmolar gap >50: suggested |
| Level on IV ethanol | Methanol >60 mg/dL (600 mg/L) | Ethylene glycol >310 mg/dL (50 mmol/L) or osmolar gap >50: recommended; 124–310 mg/dL (20–50 mmol/L) or osmolar gap 20–50: suggested |
| Level with no ADH blocker | Methanol >50 mg/dL (500 mg/L) | Ethylene glycol >62 mg/dL (10 mmol/L) or osmolar gap >10: recommended |
| Stop ECTR when | Methanol <20 mg/dL with clinical improvement | Anion gap <18 mmol/L (recommended); ethylene glycol <25 mg/dL or acid–base abnormalities corrected (suggested) |
ECTR means extracorporeal treatment. Intermittent hemodialysis is preferred, and CRRT is the option if it is unavailable. Keep giving fomepizole and folic or folinic acid during ECTR. This differs from the FDA label, which says to consider hemodialysis for renal failure, significant acidosis or a level of 50 mg/dL or more. In methanol poisoning, avoid systemic anticoagulation of the circuit where possible, because of the intracranial hemorrhage risk.
Interactions & Compatibility
Clinically Significant Interactions
| Drug / Class | Effect | What To Do |
|---|---|---|
| Ethanol (co-ingested or IV ethanol therapy) | Mutual inhibition: fomepizole cuts ethanol elimination by about 40%; ethanol cuts fomepizole elimination by about 50% | Give fomepizole anyway; expect slower clearance of both drugs and prolonged intoxication |
| CYP450 inducers and inhibitors (phenytoin, carbamazepine, cimetidine, ketoconazole) | May change fomepizole metabolism; not studied | No empiric adjustment; follow toxic alcohol levels and acid–base response |
| Acetaminophen | Fomepizole blocks CYP2E1 oxidation of acetaminophen to NAPQI | Basis for off-label use in massive overdose; never instead of acetylcysteine |
| Hemodialysis and CRRT | Remove fomepizole | Use the hemodialysis dosing rules; CRRT schedule per toxicology |
IV Compatibility
- Diluents: 0.9% sodium chloride or D5W, at least 100 mL.
- Equipment: no polycarbonate syringes or polycarbonate-containing needles.
- Y-site: the label lists no Y-site data; use a separate line or port when possible.
- Verify with an institutional compatibility resource.
Special Populations
- Pediatrics: Not FDA-established in children. Still, published pediatric cases of ethylene glycol, methanol, diethylene glycol and butoxyethanol poisoning used the adult mg/kg regimen and tolerated it well. Many of those children recovered without dialysis. Fomepizole spares the child the CNS depression of ethanol therapy, along with the frequent ethanol-level and glucose checks it demands. See the Pediatric Dosing table.
- Neonates: There are no data. Toxicologist-directed only.
- Pregnancy: There are no human or animal reproduction data. The label advises use only if clearly needed. Untreated methanol or ethylene glycol poisoning threatens both mother and fetus. Don't withhold fomepizole when poisoning is suspected.
- Lactation: It is unknown whether fomepizole enters breast milk. Use with caution, and discuss feeding timing with toxicology.
- Older Adults: The label has not established safety and effectiveness, and it gives no specific dose adjustment. Use the standard mg/kg regimen. Monitor renal and hepatic function.
- Renal Impairment: Pharmacokinetics have not been studied. Metabolites leave through the kidney, and only 1–3.5% leaves unchanged. No dose reduction is labeled. In ethylene glycol poisoning, kidney injury is itself an indication for dialysis, and the 4-hourly schedule applies on dialysis.
- Hepatic Impairment: Pharmacokinetics have not been studied. Fomepizole is cleared mainly by hepatic metabolism. The label gives no adjustment. Monitor liver enzymes.
- Obesity / Dosing Weight: The label gives mg/kg doses and names no dosing weight or maximum. Dose on actual body weight. For a patient over 100 kg, confirm the dose with pharmacy or the poison center before the loading dose.
Field & Transport Considerations
- Scope: ED, ICU and critical-care transport teams (RN, flight and critical-care paramedic) give or continue fomepizole. It is usually started in the ED, not by ground EMS. This varies by state and agency protocol.
- Storage & Stability: 20–25°C (68–77°F). It solidifies below 25°C (77°F). Warm the vial in the hand or under warm water before drawing up. Potency is not affected. Diluted bags are good for 24 hr.
- Carried Concentration: The concentration is 1 g/mL. A 15 mg/kg load for 80 kg is 1,200 mg (1.2 mL), less than one 1.5 g vial. Double-check the mg/kg and mL math.
- Infusions in Transport: Run each dose over 30 min on a pump. Know when the next dose is due. On long or delayed transfers to a dialysis center, bring the next dose along.
- Interfacility Transfer: A patient who meets EXTRIP criteria needs a center that can start hemodialysis. Give the loading dose before departure.
- Handoff Essentials: substance and time of ingestion; dosing weight; time and mg of every fomepizole dose and the next due; ethanol level; latest pH, anion gap, osmolar gap and levels; folate or thiamine given; dialysis plan.
Clinical Pearls
- Methanol turns into formic acid. That causes ocular toxicity and visual loss. Add folic or folinic acid.
- Ethylene glycol turns into glycolate and calcium oxalate. Those cause AKI, hypocalcemia and urinary crystals. Thiamine and pyridoxine are often added, though the benefit is unproven.
- Isopropanol turns into acetone. That raises the osmolar gap and causes ketosis without an anion gap acidosis. Fomepizole is not indicated, so treat supportively.
Pharmacology
Mechanism of Action
- A competitive inhibitor of alcohol dehydrogenase. It blocks the first step that turns methanol into formaldehyde and formic acid, and ethylene glycol into glycolate and oxalate.
- The parent alcohols are not very toxic themselves. They leave slowly or get removed by dialysis. Meanwhile, the metabolite-driven acidosis, blindness and kidney injury are prevented.
- It also inhibits CYP2E1, so less NAPQI forms from acetaminophen. That is the rationale for off-label use in massive overdose.
- It does nothing for metabolites already formed or for organ injury that is already established.
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV infusion | Therapeutic level expected by the end of the 30-min loading infusion (inferred; the label states no onset) | End of infusion | Dosed every 12 hr (every 4 hr during hemodialysis); the label gives no measured duration (dose-dependent elimination) |
- Half-life: Not a single value. Elimination is saturable (Michaelis-Menten) at therapeutic levels, so half-life varies with dose. Autoinduction increases clearance after 30–40 hr.
- Target level: about 10 µmol/L (0.8 mg/L) blocked methanol metabolism in monkeys (used as the minimum effective level); 100–300 µmol/L (8.6–24.6 mg/L) is targeted in humans.
- Metabolism: hepatic CYP450 oxidation; 4-carboxypyrazole is 80–85% of a dose.
- Elimination: metabolites in urine; 1–3.5% unchanged. Removed by hemodialysis and CRRT (CRRT sieving coefficient 0.85; dialysis clearance 28 mL/min in Lao 2022).
- Distribution: total body water; Vd 0.6–1.02 L/kg.
Names & Classification
- Generic Name
- Fomepizole (4-methylpyrazole, 4-MP)
- Brand Names
- Antizol (original US brand); generic fomepizole injection from several manufacturers
- Pharmacologic Class
- Alcohol dehydrogenase inhibitor
- Therapeutic Class
- Antidote (toxic alcohols)
- Controlled Substance
- Not controlled
- ISMP High-Alert
- No
- Look-Alike / Sound-Alike
- fomepizole / omeprazole (ISMP confused-name pair)
References
- Mylan Institutional. (2021). Fomepizole injection [prescribing information] (revised April 2021). DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=911312e2-3a7c-4c97-88a8-b8d92cd12923
- Ghannoum, M., Gosselin, S., Hoffman, R. S., Lavergne, V., Mégarbane, B., Hassanian-Moghaddam, H., Rif, M., Kallab, S., Bird, S., Wood, D. M., Roberts, D. M., for the EXTRIP Workgroup. (2023). Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup. Critical Care, 27, 56. https://doi.org/10.1186/s13054-022-04227-2
- Roberts, D. M., Yates, C., Megarbane, B., Winchester, J. F., Maclaren, R., Gosselin, S., Nolin, T. D., Lavergne, V., Hoffman, R. S., Ghannoum, M., EXTRIP Work Group. (2015). Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement (current EXTRIP methanol recommendations; landmark consensus). Critical Care Medicine, 43(2), 461–472. https://doi.org/10.1097/CCM.0000000000000708
- Dart, R. C., Mullins, M. E., Matoushek, T., Ruha, A. M., Burns, M. M., Simone, K., Beuhler, M. C., Heard, K. J., Mazer-Amirshahi, M., Stork, C. M., Varney, S. M., Funk, A. R., Cantrell, L. F., Cole, J. B., Banner, W., Stolbach, A. I., Hendrickson, R. G., Lucyk, S. N., Sivilotti, M. L. A., Su, M. K., Nelson, L. S., & Rumack, B. H. (2023). Management of acetaminophen poisoning in the US and Canada: a consensus statement. JAMA Network Open, 6(8), e2327739. https://doi.org/10.1001/jamanetworkopen.2023.27739
- Lao, Y. E., Vartdal, T., Froeyshov, S., Latimer, B., Kvaerner, C., Mataric, M., Holm, P., Foreid, S., Jacobsen, D., McMartin, K., & Hovda, K. E. (2022). Fomepizole dosing during continuous renal replacement therapy: an observational study. Clinical Toxicology, 60(4), 451–457. https://doi.org/10.1080/15563650.2021.1980581
- Kang, A. M., Padilla-Jones, A., Fisher, E. S., Akakpo, J. Y., Jaeschke, H., Rumack, B. H., Gerkin, R. D., & Curry, S. C. (2020). The effect of 4-methylpyrazole on oxidative metabolism of acetaminophen in human volunteers. Journal of Medical Toxicology, 16(2), 169–176. https://doi.org/10.1007/s13181-019-00740-z
- Brent, J. (2010). Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings (landmark pediatric case review). Clinical Toxicology, 48(5), 401–406. https://doi.org/10.3109/15563650.2010.495347
- Institute for Safe Medication Practices. (2024). ISMP list of confused drug names (updated through June 2024). https://online.ecri.org/hubfs/ISMP/Resources/ISMP_ConfusedDrugNames.pdf
- EXTRIP Workgroup. (2019). Methanol: ECTR recommendations (EXTRIP website). https://www.extrip-workgroup.org/methanol
Medical Disclaimer
- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
- Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
- Verify Before Acting: Users are responsible for verifying information through authoritative sources before any clinical application.