Fomepizole Dose Calculator

Fomepizole Dose Calculator

Work out a single fomepizole dose in milligrams from body weight and the step of the schedule — 15 mg/kg to load, 10 mg/kg for four doses, then 15 mg/kg — and see why the frequency goes up during haemodialysis.

Fomepizole single dose

Weight → dose
Use actual body weight. Fomepizole is dosed in mg/kg at every step of the schedule.
The dose falls to 10 mg/kg for the first four maintenance doses and then returns to 15 mg/kg, because fomepizole induces its own metabolism after about 48 hours. During haemodialysis the size of the dose does not change but the frequency does: give it every 4 hours.
1,050mg for this doseExample

A 70 kg adult, loading dose at 15 mg/kg

The schedule

Dose (mg) = body weight (kg) × mg/kg for this step
Loading 15 mg/kg · then 10 mg/kg every 12 hours for 4 doses · then 15 mg/kg every 12 hours
During haemodialysis: give every 4 hours
15 mg/kg loading
the first dose, given as a slow intravenous infusion over 30 minutes and started as soon as poisoning is suspected — not when a level returns
10 mg/kg × 4
the next four doses, 12 hours apart. The dose is lower than the load because a loading dose is by definition larger than the doses that maintain the concentration
15 mg/kg thereafter
from the fifth maintenance dose, 48 hours in, the dose goes back up. Fomepizole induces its own metabolism through cytochrome P450, so clearance increases and a larger dose is needed to hold the same concentration
every 4 hours during haemodialysis
fomepizole is a small, water-soluble, minimally protein-bound molecule and is removed efficiently by dialysis. Leaving the 12-hourly schedule alone during dialysis allows the block on alcohol dehydrogenase to lapse at the very moment the patient is sickest
the endpoint
per the label, treatment may stop when the ethylene glycol or methanol concentration is undetectable or below 20 mg/dL <b>and</b> the patient is asymptomatic with a normal pH — all three, not the level alone
what it does not do
fomepizole prevents further toxic metabolite being formed. It does nothing to the formate, glycolate or oxalate already made; removing those is what haemodialysis is for

Worked example

A 70 kg adult, loading dose at 15 mg/kg
15 × 70 = 1050 mg, as a slow intravenous infusion over 30 minutes in at least 100 mL of diluent
The next four doses are 10 × 70 = 700 mg, 12 hours apart
From the fifth maintenance dose — about 48 hours in — the dose returns to 15 × 70 = 1050 mg every 12 hours, because fomepizole induces its own metabolism
If this patient goes on haemodialysis, the dose size is unchanged but the interval shortens to every 4 hours, because dialysis removes fomepizole as efficiently as it removes the alcohol
At the start of dialysis: give the next scheduled dose if more than 6 hours have passed since the last one, and withhold it if less than 6 hours have
Stop when the alcohol is undetectable or below 20 mg/dL and the patient is asymptomatic with a normal pH — the level alone is not the endpoint, and it was not the trigger either

The schedule at three common weights

Stepmg/kg50 kg70 kg100 kg
Loading dose15750 mg1050 mg1500 mg
Maintenance doses 1–4, 12-hourly10500 mg700 mg1000 mg
Maintenance dose 5 onwards, 12-hourly15750 mg1050 mg1500 mg
Any dose during haemodialysisas aboveas above, every 4 hoursas above, every 4 hoursas above, every 4 hours
Every dose is a slow intravenous infusion over 30 minutes, diluted in at least 100 mL of 0.9% sodium chloride or 5% dextrose; fomepizole should not be given as a bolus or undiluted. The rise back to 15 mg/kg at the fifth maintenance dose is easy to miss and is the commonest prescribing error with this drug.

Dosing around haemodialysis

MomentWhat to do
During dialysisGive the dose every 4 hours instead of every 12 — fomepizole is dialysed out
At the start of dialysis, less than 6 hours since the last doseDo not give a dose
At the start of dialysis, more than 6 hours since the last doseGive the next scheduled dose
When dialysis finishesReturn to the 12-hourly schedule, timed from the last dose given
Ethanol as the alternative blockerWhere fomepizole is unavailable, the ethanol infusion rate must likewise be increased during dialysis, and a target blood ethanol of around 100 mg/dL needs frequent monitoring
This is the part of fomepizole prescribing most often got wrong, and the consequence is specific: the alcohol dehydrogenase block lapses mid-dialysis and toxic metabolite production resumes in a patient who is already acidotic. The interval, not the dose, is what changes.

What fomepizole does, and what it cannot

FomepizoleHaemodialysis
MechanismCompetitive inhibition of alcohol dehydrogenasePhysical removal across a membrane
Stops more toxic metabolite formingYesIndirectly, by removing the substrate
Removes metabolite already formedNoYes — formate, glycolate
Corrects the acidosisNoYes
Effect on the parent alcohol levelIt stops falling — the half-life lengthens to many hours, which is expected and not treatment failureIt falls quickly
AvailabilityA drug, given anywhere, immediatelyNeeds a dialysis service, access and time
The two do different jobs and the sequencing follows from that. Blocking the enzyme early is what prevents injury, so fomepizole is given on suspicion — on a history, an unexplained high anion gap acidosis or a raised osmolal gap — long before any concentration is available. Dialysis deals with what has already been formed.

Block the enzyme early, and remember the interval on dialysis

Fomepizole (4-methylpyrazole) is a competitive inhibitor of alcohol dehydrogenase, the enzyme that turns methanol into formaldehyde and then formic acid, and ethylene glycol into glycolaldehyde, glycolic acid and oxalic acid. Since the parent alcohols are relatively harmless and the acids are what cause blindness, acidosis and renal failure, blocking that enzyme stops the poisoning progressing. It is the reason the drug works, and it is also the reason it has to be given early: fomepizole prevents metabolite being made, and does nothing whatever about metabolite already made. Formate and glycolate that have already formed are removed by haemodialysis, not by the antidote.

The schedule is a loading dose of 15 mg/kg, then 10 mg/kg every 12 hours for four doses, then 15 mg/kg every 12 hours thereafter, each given as a slow intravenous infusion over 30 minutes and diluted in at least 100 mL of 0.9% sodium chloride or 5% dextrose. The step back up to 15 mg/kg at about 48 hours is not arbitrary and it is the part most often missed: fomepizole induces its own metabolism through cytochrome P450, so its clearance increases over the first two days and a larger dose is needed to hold the same degree of enzyme blockade. Vials solidify below about 25°C, which alarms people who have not seen it before; the solid is liquefied by running the vial under warm water or holding it, and the drug is unaffected.

The second thing to get right is haemodialysis. Fomepizole is small, water-soluble and barely protein-bound, so it is cleared by dialysis about as efficiently as the alcohol it is blocking. Left on the 12-hourly schedule, the antidote is dialysed away mid-session and the enzyme unblocks at the moment the patient can least afford it. The dose size does not change; the frequency increases to every four hours for as long as dialysis continues. At the start of a session, give the next scheduled dose if more than six hours have passed since the last, and withhold it if fewer than six have. When dialysis finishes, return to 12-hourly timed from the last dose given. The same principle applies to an ethanol infusion where fomepizole is not held: the rate has to be increased during dialysis.

Two things this calculator does not do. It does not decide whether to treat. The antidote is started on clinical suspicion — a plausible history, an unexplained wide anion gap metabolic acidosis, a raised osmolal gap, visual symptoms — because most hospitals cannot measure methanol or ethylene glycol in a timeframe that would make a level useful, and because the harm is done while the result is awaited. The published concentration threshold of 20 mg/dL is one indication among several, and the others deliberately require no level at all. Nor does it decide when to stop: the label’s endpoint is that the alcohol concentration is undetectable or below 20 mg/dL and the patient is asymptomatic with a normal pH, and that judgement, like the decision to dialyse, belongs to the treating team with critical care, nephrology and the national poisons service. See the methanol and ethylene glycol converters for the thresholds, and note that isopropanol poisoning needs no fomepizole at all.

Frequently asked questions

What is the fomepizole dosing schedule?

A loading dose of 15 mg/kg, then 10 mg/kg every 12 hours for four doses, then 15 mg/kg every 12 hours thereafter, each as a slow intravenous infusion over 30 minutes in at least 100 mL of diluent. For a 70 kg adult that is 1050 mg, then 700 mg twelve-hourly for four doses, then 1050 mg twelve-hourly. During haemodialysis the dose is given every 4 hours instead of every 12.

Why does the dose go back up to 15 mg/kg after four maintenance doses?

Because fomepizole induces its own metabolism. Over the first 48 hours of treatment its clearance increases through cytochrome P450 induction, so the 10 mg/kg dose that maintained an inhibitory concentration at the start no longer does. Returning to 15 mg/kg from the fifth maintenance dose compensates. Missing this step is the commonest prescribing error with the drug and leaves the enzyme partially unblocked.

Does the fomepizole dose change during haemodialysis?

The dose size does not, but the frequency does: give it every 4 hours for as long as dialysis continues, because fomepizole is small, water-soluble and minimally protein-bound and is removed efficiently by the dialyser. At the start of a session, give the next scheduled dose if more than 6 hours have elapsed since the last one and withhold it if fewer than 6 have. Afterwards, resume 12-hourly dosing timed from the last dose given.

Do you wait for a methanol or ethylene glycol level before giving fomepizole?

No. Most hospitals cannot measure either alcohol, and those that can rarely report within the window in which blocking the enzyme prevents injury. The antidote is started on clinical suspicion: a plausible history, an unexplained wide anion gap metabolic acidosis, a raised osmolal gap, or visual symptoms. The published 20 mg/dL threshold is one indication among several and the guideline’s other limbs deliberately need no concentration at all.

Why does the alcohol level stop falling once fomepizole is running?

Because that is what the drug does. With alcohol dehydrogenase blocked, methanol and ethylene glycol are no longer metabolised and clear only slowly by renal and pulmonary routes, so their half-lives lengthen to many hours. A persistently high level on fomepizole is evidence that the block is working, not that treatment is failing. What it does mean is that the parent alcohol will take a long time to disappear, which is one of the considerations in deciding whether to dialyse.

Is fomepizole used for isopropanol or ethanol poisoning?

No. Isopropanol is metabolised to acetone, a ketone rather than an acid, so there is no toxic metabolite to prevent and blocking the enzyme simply prolongs the sedation; management is supportive. Ethanol poisoning is likewise managed supportively. Fomepizole is for methanol and ethylene glycol, where the parent alcohol is comparatively harmless and the metabolites are what cause the injury.

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References

  1. Fomepizole injection, USP — prescribing information. DailyMed, US National Library of Medicine. “A loading dose of 15 mg/kg should be administered, followed by doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours thereafter”; all doses as a slow intravenous infusion over 30 minutes; dose every 4 hours during haemodialysis; treatment may be discontinued when ethylene glycol or methanol concentrations are undetectable or below 20 mg/dL and the patient is asymptomatic with a normal pH.
  2. Brent J, McMartin K, Phillips S, et al; Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of ethylene glycol poisoning. N Engl J Med. 1999;340(11):832–838.
  3. Brent J, McMartin K, Phillips S, Aaron C, Kulig K; Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of methanol poisoning. N Engl J Med. 2001;344(6):424–429.
  4. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415–446.
  5. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol. 1999;37(5):537–560.

Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.