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Frequently-asked questions about Antizol (fomepizole)
Injection
What is Antizol’s
mechanism of action?
When should Antizol
treatment begin?
Should the Antizol
dosing be changed if ethanol is present?
Should serum
fomepizole concentrations be monitored during Antizol treatment?
Can Antizol be administered
orally?
When should treatment
of Antizol be discontinued?
What is the half-life
of Antizol?
How should Antizol be
dosed during Continuous Veno-Venous Hemofiltration?
What happens
if Antizol is administered to a patient who has not ingested ethylene
glycol or methanol?
Why is the dose
of Antizol increased after 36 hours?
How much Antizol is
required to treat a patient?
Can Antizol be used
for ethylene glycol or methanol poisoning in children?
Can Antizol be used
to treat other toxic alcohols?
I have urgent need
of Antizol. How can I obtain it?
How should Antizol
be dosed during hemodialysis?
Q: What is
Antizol’s mechanism of action?
A: Fomepizole
is a competitive inhibitor of alcohol dehydrogenase, which normally
oxidizes ethylene glycol and methanol to their respective toxic
metabolites.
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Q:
When should Antizol treatment begin?
A: Begin Antizol treatment
immediately upon proof or suspicion of ethylene glycol or methanol
ingestion based on patient history, associated signs and symptoms
OR a measured serum ethylene glycol or methanol concentration greater
than 20 mg/dL.
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Q: Should
the Antizol dosing be changed if ethanol is present?
A: Ethanol therapy is often
initiated prior to transporting a methanol or ethylene glycol-poisoned
patient to a referral hospital. Because fomepizole is considered
a more effective inhibitor of alcohol dehydrogenase than ethanol,
Antizol administration should be immediately initiated at normally
recommended doses.
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Q: Should
serum fomepizole concentrations be monitored during Antizol treatment?
A: The recommended dosing schedule
maintains serum fomepizole concentrations in excess of 10 mmol/L,
the minimum inhibitory concentration for alcohol dehydrogenase.
This assures adequate alcohol dehydrogenase inhibition without the
need for monitoring serum fomepizole concentrations.
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Q: Can
Antizol be administered orally?
A: Antizol has been approved by
the FDA for intravenous use only. This route was chosen during drug
development as the best suited for the greatest number of clinical
situations. There are reports of orally administered fomepizole
in the literature and it appears to be highly bioavailable by that
route.
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Q: When
should treatment of Antizol be discontinued?
A: Antizol may be discontinued
when serum ethylene glycol or methanol concentrations are undetectable
OR have been reduced below 20 mg/dL AND the patient is asymptomatic
with normal pH.
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Q: What
is the half-life of Antizol?
A: The elimination of fomepizole
obeys zero-order kinetics at therapeutic doses. Thus, a serum half-life
cannot be calculated.
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Q: How
should Antizol be dosed during Continuous Veno-Venous Hemofiltration?
A: Fomepizole kinetics under conditions
of CVVH have not been studied and specific dosing recommendations
cannot be made. Anecdotally, Jazz Pharmaceuticals is aware of ethylene
glycol-poisoned patients who have received Antizol while undergoing
CVVH. In those cases, hemodialysis dosing guidelines for Antizol
were used.
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Q: What
happens if Antizol is administered to a patient who has not ingested
ethylene glycol or methanol?
A: Fomepizole has been administered
to normal human volunteers. Therapeutic doses produced nausea, headache,
dizziness and unpleasant taste in some instances.
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Q: Why
is the dose of Antizol increased after 36 hours?
A: Following the administration
of multiple doses, fomepizole induces its own metabolism via the
cytochrome P-450 mixed-function oxidase system. This causes a significant
increase in fomepizole metabolism after 30-40 hours. Increasing
the maintenance dose to 15 mg/kg every 12 hours will maintain therapeutic
plasma concentrations of fomepizole after 36 hours.
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Q:
How much Antizol is required to treat a patient?
A: Antizol is supplied in packages
of four vials, each containing 1.5 gm fomepizole (1gm/ml). Unless
the patient undergoes hemodialysis, a 4-vial tray pack of Antizol
should be sufficient to treat a 70 kg person.
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Q: Can
Antizol be used for ethylene glycol or methanol poisoning in children?
A: The FDA has approved Antizol
for use in adults only; however, there are published reports of
Antizol use in children using adult dosing guidelines.
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Q:
Can Antizol be used to treat other toxic alcohols?
A: Antizol is contraindicated
for the treatment of isopropanol poisoning. Isopropanol is metabolized
to acetone which is less toxic that isopropanol and excreted renally.
The presence of fomepizole will only prolong the period of isopropanol
intoxication. While formal studies have not been conducted, there
are published reports of successful treatment of diethylene glycol
poisoning with fomepizole.
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Q:
I have urgent need of Antizol. How can I obtain it?
A: Under normal circumstances,
Antizol is received one business day after ordering. If the need
is urgent, a regional poison control center may be able to help
identify local sources.
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Q: How
should Antizol be dosed during hemodialysis?
A: As fomepizole is removed by
hemodialysis, patients undergoing this procedure must receive Antizol
more frequently. The dosing interval during hemodialysis is every
4 hours. The following schedule should be used to determine the
timing for Antizol dosing:
• AT THE BEGINNING
OF HEMODIALYSIS,
do not administer if < 6 hours since the last dose; or
administer the next dose if ≥ 6 hours since the last dose.
• DURING CONTINUOUS
HEMODIALYSIS,
administer every 4 hours.
• AT THE END
OF HEMODIALYSIS,
do not administer if the time between the last dose and the end
of dialysis is < 1 hour; or
administer ½ the next dose if the time between the last dose
and the end of dialysis is 1-3 hours; or
administer the next full dose if the time between the last dose
and the end of dialysis is > 3 hours.
• FOLLOWING HEMODIALYSIS,
resume administration every 12 hours.
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