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FOMEPIZOLE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Fomepizole is a competitive inhibitor of alcohol dehydrogenase (ADH).

Specific Substances

    1) 4-Methyl-1H-pyrazole
    2) 4-Methylpyrazole
    3) 4-MP
    4) Methylpyrazole
    5) Molecular Formula: C4-H6-N2
    6) CAS 7554-65-6

Available Forms Sources

    A) FORMS
    1) Fomepizole is available as a sterile, preservative-free solution for intravenous use. Each vial contains 1.5 mL (1 g/mL) of fomepizole (Prod Info fomepizole intravenous injection, 2012).
    B) USES
    1) Fomepizole is used in the treatment of poisoning by ethylene glycol or methanol (Prod Info fomepizole intravenous injection, 2012). It prevents and reverses the development of metabolic acidosis and renal failure by blocking the accumulation of toxic metabolites.
    2) Fomepizole has been used to treat the disulfiram-ethanol reaction, although it is not currently approved for this indication. Fomepizole prevents the metabolism of ethanol to acetaldehyde by inhibiting alcohol dehydrogenase (Kuffner, 2006; Lindros et al, 1981). In one study, fomepizole was able to inhibit alcohol dehydrogenase and block the accumulation of acetaldehyde that accompanies disulfiram use and its characteristic symptoms (ie, intense flushing and tachycardia) (Lindros et al, 1981).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Fomepizole is an antidote primarily used for ethylene glycol and methanol poisoning.
    B) PHARMACOLOGY: Fomepizole has been shown to block alcohol dehydrogenase activity, preventing the metabolism of toxic byproducts from ethylene glycol (glycolate and oxalate) and methanol (formic acid).
    C) EPIDEMIOLOGY: Overdose from the use of fomepizole is rare.
    D) TOXICITY: At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term.
    E) WITH THERAPEUTIC USE
    1) COMMON: Headache, nausea, dizziness, increased drowsiness, and metallic taste. LESS COMMON: Skin irritation at the site of administration, vomiting, diarrhea, dyspepsia, decreased appetite, bradycardia, tachycardia, hypotension, rash, feeling drunk, anxiety, mild elevation of liver enzymes, seizures, vision/speech disturbance, disseminated intravascular coagulation, and anemia.
    F) WITH POISONING/EXPOSURE
    1) At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term.
    0.2.20) REPRODUCTIVE
    A) It is not known if fomepizole causes fetal harm. Fomepizole should only be given to pregnant women when clearly indicated. It is not known if fomepizole is excreted in human milk.

Laboratory Monitoring

    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring.
    C) Monitor electrolytes in patients with severe vomiting and/or diarrhea or significant overdose.
    D) Monitor renal function and liver enzymes after large overdose.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) At the time of this review, no reports of inadvertent overdose with fomepizole have been published. The adverse effects were short-term and mild when healthy volunteers were given supratherapetuic doses fomepizole.
    B) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive.
    C) MANAGEMENT OF SEVERE TOXICITY
    1) Treat hypotension with fluids and vasopressors, if necessary. Treat bradycardia with atropine, if unresponsive, use beta adrenergic agonists (eg, isoproterenol).
    D) DECONTAMINATION
    1) Decontamination is not necessary, fomepizole is administered parenterally.
    E) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and preform endotracheal intubation early in patients with serious cardiac toxicity or respiratory depression.
    F) ANTIDOTE
    1) None.
    G) BRADYCARDIA
    1) Atropine; if unresponsive, use beta adrenergic agonists (eg, isoproternol).
    H) HYPOTENSIVE EPISODE
    1) IV NS 10 to 20 ml/kg, dopamine, norepinephrine.
    I) ENHANCED ELIMINATION PROCEDURE
    1) Fomepizole is dialyzable and hemodialysis may have value in the treatment of an overdose.
    J) PATIENT DISPOSITION
    1) OBSERVATIONAL CRITERIA: Overdose is likely to be iatrogenic error in patients already admitted to the hospital. Patients should be observed in a healthcare facility and monitored until symptoms resolve.
    2) ADMISSION CRITERIA: Patients demonstrating cardiotoxicity should be admitted to an intensive care setting.
    3) CONSULT CRITERIA: Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity (ie, bradycardia) or in whom the diagnosis is unclear.
    K) PHARMACOKINETICS
    1) Fomepizole is rapidly distributed into total body water following intravenous infusion and the approximate volume of distribution is between 0.6 L/kg and 1.02 L/kg. Hepatic metabolism is the major route of elimination and small studies suggest the mean elimination half-life is approximately 14.5 +/- 3 hours, without concomitant ethanol administration or dialysis.
    L) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause bradycardia or hypotension (beta-blockers, vasodilators, calcium channel blockers).
    M) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    N) ATROPINE: ADULT DOSE: BRADYCARDIA: BOLUS: 0.5 mg IV may repeat every 3 to 5 min. Maximum: 3 mg. PEDIATRIC DOSE: 0.02 mg/kg IV/IO (0.04 to 0.06 mg/kg ET). Repeat once, if needed. Minimum dose: 0.1 mg. Maximum single dose: Child: 0.5 mg; Adolescent: 1 mg. Maximum total dose: Child: 1 mg; Adolescent: 2 mg.

Range Of Toxicity

    A) TOXICITY: At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term. THERAPEUTIC DOSE: Give 15 mg/kg initially, followed by 10 mg/kg every 12 hours for 4 doses, and increase to 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL and the patient is asymptomatic with normal pH. All doses should be administered as a slow IV infusion over 30 minutes.

Clinical Effects

Summary Of Exposure

    A) USES: Fomepizole is an antidote primarily used for ethylene glycol and methanol poisoning.
    B) PHARMACOLOGY: Fomepizole has been shown to block alcohol dehydrogenase activity, preventing the metabolism of toxic byproducts from ethylene glycol (glycolate and oxalate) and methanol (formic acid).
    C) EPIDEMIOLOGY: Overdose from the use of fomepizole is rare.
    D) TOXICITY: At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term.
    E) WITH THERAPEUTIC USE
    1) COMMON: Headache, nausea, dizziness, increased drowsiness, and metallic taste. LESS COMMON: Skin irritation at the site of administration, vomiting, diarrhea, dyspepsia, decreased appetite, bradycardia, tachycardia, hypotension, rash, feeling drunk, anxiety, mild elevation of liver enzymes, seizures, vision/speech disturbance, disseminated intravascular coagulation, and anemia.
    F) WITH POISONING/EXPOSURE
    1) At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Visual disturbances, transient blurred vision, and nystagmus have been reported in some individuals following therapeutic use (Prod Info ANTIZOL(R) IV injection, 2006).
    2) NYSTAGMUS: Transient coarse vertical nystagmus began within 2 hours of fomepizole (a loading dose of 15 mg/kg was infused over 30 minutes) administration and lasted approximately an hour in a 6-year-old comatose female who had ingested ethylene glycol. No other adverse effects were reported and the child recovered uneventfully within 48 hours of admission (Benitez et al, 2000).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH THERAPEUTIC USE
    a) Bradycardia, tachycardia, and hypotension have been reported during therapeutic use in 3% or less of patients or healthy volunteers. Other rare effects have included phlebosclerosis and shock (Prod Info ANTIZOL(R) IV injection, 2006). These effects may be due to the underlying disorder being treated rather than the fomepizole therapy.
    b) In one case report, the occurrence of bradycardia following fomepizole use could not be directly related to therapy (Brent et al, 1999).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) In 78 patients and 63 healthy volunteers, headache (14%), dizziness (6%), and increased drowsiness (6%) were the most frequently reported adverse effects during therapeutic use (Prod Info ANTIZOL(R) IV injection, 2006). In one study of healthy volunteers, dizziness was consistently reported and presumed to be dose-related (Jacobsen et al, 1988).
    b) In the same population, seizures, agitation, feeling inebriated, vertigo, anxiety, and decreased awareness were reported in 3% or less of individuals (Prod Info ANTIZOL(R) IV injection, 2006).
    c) In one case report, the occurrence of seizures following fomepizole use could not be directly related to therapy (Brent et al, 1999).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH THERAPEUTIC USE
    a) In 78 patients and 63 healthy volunteers, nausea (11%) was reported with therapeutic fomepizole use (Prod Info ANTIZOL(R) IV injection, 2006).
    B) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH THERAPEUTIC USE
    a) In 78 patients and 63 healthy volunteers, vomiting, diarrhea, dyspepsia, heartburn, and decreased appetite were reported in 3% or less of individuals receiving therapeutic doses of fomepizole (Prod Info ANTIZOL(R) IV injection, 2006). Other clinical studies have reported similar findings (Jacobsen et al, 1990).
    b) UNPLEASANT TASTE has been reported in clinical studies using the freebase liquid (>99.5% purity) form of fomepizole (Jacobsen et al, 1990; Jacobsen et al, 1988) . Metallic taste has also been reported following intravenous therapy with fomepizole (Shannon, 1998).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) A transient increase in serum transaminase (AST) levels has occurred after receiving fomepizole therapy in ethanol- and ethylene glycol-intoxicated patients (Harry et al, 1994; Jacobsen et al, 1990) .
    b) INCIDENCE: In 40% of healthy volunteers, transient elevations in serum transaminase levels (SGPT and/or SGOT levels) were reported following multiple dosing with fomepizole. The effects did not appear dose-related or due to a hypersensitivity reaction (Jacobsen et al, 1990).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH THERAPEUTIC USE
    a) Eosinophilia was possibly associated with fomepizole use in a patient intoxicated with ethylene glycol (Baud et al, 1986). Other hematological adverse effects that have been reported in 3% or less of patients receiving fomepizole have included disseminated intravascular coagulation and anemia (Prod Info ANTIZOL(R) IV injection, 2006).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Rash with pruritus has been reported infrequently following therapeutic use of fomepizole (Prod Info ANTIZOL(R) IV injection, 2006)Baud et al, 1986 .
    B) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) Intravenous administration has resulted in skin irritation and injection site reaction of the affected vein (Prod Info ANTIZOL(R) IV injection, 2006).

Reproductive

    3.20.1) SUMMARY
    A) It is not known if fomepizole causes fetal harm. Fomepizole should only be given to pregnant women when clearly indicated. It is not known if fomepizole is excreted in human milk.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Pregnancy Category C (Prod Info Antizol(R), fomepizole , 2000)
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is not known if fomepizole is excreted in human milk (Prod Info Antizol(R), fomepizole , 2000).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) Currently, there have been no long-term animal studies to evaluate carcinogenic potential (Prod Info Antizol(R), fomepizole , 2000).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring.
    C) Monitor electrolytes in patients with severe vomiting and/or diarrhea or significant overdose.
    D) Monitor renal function and liver enzymes after large overdose.
    4.1.2) SERUM/BLOOD
    A) BLOOD SERUM/CHEMISTRY
    1) Monitor renal function and liver enzymes following significant overdose. Transient elevations in serum transaminase levels have occurred with therapy.
    2) Monitor electrolytes and fluid status following significant gastrointestinal loss or after significant overdose.
    B) HEMATOLOGIC
    1) Hematologic abnormalities (e.g., eosinophilia, anemia) are infrequent during therapy. Monitor as indicated following significant exposure.

Methods

    A) CHROMATOGRAPHY
    1) Fomepizole has been analyzed in plasma and urine by a modified high performance liquid chromatography method (Jacobsen et al, 1990; Jacobsen & McMartin, 1996). The modification consisted of the addition of 3-methylpyrazole, an internal standard, to the sample prior to the extraction (Jacobsen et al, 1990).
    2) Gas chromatography with nitrogen phosphorous detection was used to determine fomepizole concentrations in human blood and tissue. The limits of detection and quantification, using this method, were 0.2 and 0.5 mcg/mL, respectively (Wallemacq et al, 2004).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients demonstrating cardiotoxicity should be admitted to an intensive care unit.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity (ie, bradycardia) or in whom the diagnosis is unclear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Overdose is likely to be iatrogenic error in patients already admitted to the hospital. Patients should be observed in a healthcare facility and monitored until symptoms resolve.

Monitoring

    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring.
    C) Monitor electrolytes in patients with severe vomiting and/or diarrhea or significant overdose.
    D) Monitor renal function and liver enzymes after large overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Fomepizole is administered parenterally; oral decontamination is not necessary.

Range Of Toxicity

Summary

    A) TOXICITY: At the time of this review, no reports of inadvertent overdose with fomepizole have been published. In healthy volunteers receiving 50 and 100 mg/kg doses (3 to 6 times the recommended dose) of fomepizole, nausea, dizziness, and vertigo were reported. In most individuals, the effects were short-term. THERAPEUTIC DOSE: Give 15 mg/kg initially, followed by 10 mg/kg every 12 hours for 4 doses, and increase to 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL and the patient is asymptomatic with normal pH. All doses should be administered as a slow IV infusion over 30 minutes.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) SUMMARY: Fomepizole is started immediately after ethylene glycol or methanol ingestion is suspected based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine OR a serum ethylene glycol or methanol concentration greater than 20 mg/dL (Prod Info fomepizole intravenous injection, 2012).
    2) LOADING DOSE: A loading dose of 15 mg/kg is given, which is diluted in at least 100 mL of sterile 0.9% sodium chloride injection or dextrose 5% injection. Infuse over 30 minutes (Prod Info fomepizole intravenous injection, 2012).
    3) Follow initial dose by giving doses of 10 mg/kg every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol or methanol concentrations are undetectable or have been reduced to below 20 mg/dL. All doses should be given by slow intravenous infusion over approximately 30 minutes (Prod Info fomepizole intravenous injection, 2012). The goal of therapy is a normal pH with no symptoms (i.e., to prevent further metabolism of ethylene glycol or methanol to their toxic metabolites) (Prod Info fomepizole intravenous injection, 2012).
    4) DOSING WITH RENAL DIALYSIS: Fomepizole is dialyzable. Dosing should be increased to every 4 hours if hemodialysis is required and continued every 4 hours during dialysis (Prod Info fomepizole intravenous injection, 2012).
    a) DOSING WHEN HEMODIALYSIS IS COMPLETED: If less than 1 hour since the last dose and the end of dialysis, do NOT administer fomepizole dose at the end of dialysis; at 1 to 3 hours give one-half of the next scheduled dose and if greater than 3 hours give the next scheduled dose of fomepizole (Prod Info fomepizole intravenous injection, 2012).
    b) MAINTENANCE DOSE OFF HEMODIALYSIS: Give next scheduled dose 12 hours from the last dose administered (Prod Info fomepizole intravenous injection, 2012).
    5) HYDRATION: High urine output through forced diuresis is recommended during therapy to enhance the elimination of unmetabolized ethylene glycol in urine to shorten the overall length of treatment (Shannon, 1998).
    B) DISEASE STATE
    1) DISULFIRAM-ALCOHOL REACTION
    a) In one study, fomepizole was used in the treatment of a disulfiram-alcohol reaction. Fomepizole was able to inhibit alcohol dehydrogenase and block the accumulation of acetaldehyde that accompanies disulfiram use and its characteristic symptoms (i.e., intense flushing and tachycardia). It also appears to prevent the excess formation of acetaldehyde (Lindros et al, 1981).
    1) Blood acetaldehyde levels immediately (within minutes) normalized along with the gradual decline in symptoms (facial flushing and tachycardia) after receiving fomepizole (7 mg/kg intravenously) in an adult with a history of chronic alcohol abuse who had consumed alcohol and disulfiram. The authors suggested that this relatively small dose had also been used effectively in other acute clinical settings (Lindros et al, 1981).
    7.2.2) PEDIATRIC
    A) GENERAL
    1) Safety and efficacy have not been established in pediatric patients (Prod Info fomepizole intravenous injection, 2012). However, several pediatric case reports of successful use of fomepizole have been documented in the literature (Baum et al, 2000; Brophy et al, 2000; Boyer et al, 2001).
    B) PEDIATRIC USE-
    1) INFANT: An 8 month old 7.7 kg male drank up to 120 mL of 95% ethylene glycol after unintentional transfer of antifreeze to the infant's bottle. The patient became lethargic and was intubated. An ethanol infusion was begun. Laboratory studies indicated an anion gap of 12.5, a pH of 7.32, an initial serum EG concentration of 384 mg/dL, and an initial urinalysis (approximately 4 hours after ingestion; total dose 45 mg/kg) revealed significant calcium oxalate crystals (Baum et al, 2000).
    a) Following consent, fomepizole was given at a loading dose of 15 mg/kg and hemodialysis was started (total time 4 hours), which reduced the serum EG concentration to 61 mg/dL and reduced serum osmolality. During dialysis fomepizole dosing was modified based on manufacturers recommendations and given every 4 hours. Despite some hematuria, renal function remained normal. Fomepizole allowed for the correction of metabolic acidosis. No further complications related to the ingestion were reported and the infant recovered within 45 hours postingestion (Baum et al, 2000).
    2) TODDLER: A 17-month-old (10-kg) female ingested an unknown amount of brake fluid containing diethylene glycol and received a one-time dose of fomepizole (15 mg/kg {150 mg total}) intravenously along with hemodialysis. No untoward effects were reported from this drug therapy (Brophy et al, 2000).
    3) ADOLESCENT: A 13-year-old female (80 kg) ingested 120 mL of ethylene glycol and was treated successfully with fomepizole. Approximately 30 minutes after ingestion, the patient was brought to an emergency department and had an anion gap of 14 mg/dL, pH 7.38, PCO2 38 mmHg, and PO2 116 mmHg, and a serum ethylene glycol concentration of 103 mg/dL; toxicology screen was negative. Ataxia and dysarthria occurred and the patient was started on an intravenous ethanol bolus of 600 mg/kg followed by a continuous infusion. Immediately following the bolus, intubation was required due to further CNS depression (Boyer et al, 2001).
    a) Six hours after ingestion, the patient received a 15 mg/kg intravenous loading dose of fomepizole and was successfully extubated 12 hours later with a stable pH. Therapy was continued at 10 mg/kg every 12 hours for a total of 5 doses. The patient was discharged to home on the third day with no permanent sequelae (Boyer et al, 2001).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) At the time of this review, no overdose data are available(Prod Info fomepizole intravenous injection, 2012) .

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Healthy individuals have tolerated intravenous fomepizole doses of 50 and 100 mg/kg (3 to 6 times the recommended dose) with minimal adverse effects. Symptoms were limited to nausea, dizziness and vertigo (Jacobsen et al, 1988; Prod Info fomepizole intravenous injection, 2012).
    B) ANIMAL DATA
    1) In mice studies, high doses (400 mg/kg) of fomepizole produced drowsiness, inhibition of exploration, and unsteady gait. Doses of 650 to 1400 mg/kg produced a LD50 value for mice and rats with sedative and hypnotic effects present (Jacobsen et al, 1988).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Fomepizole is a potent inhibitor of alcohol dehydrogenase (ADH) activity; it has an affinity for ADH which is 8,000 times greater than ethanol and 80,000 times greater than methanol in in vitro studies (Jacobsen & McMartin, 1996; Shannon, 1998; Hazouard et al, 2000). ADH catalyzes the oxidation of ethanol to acetaldehyde, as well as, acting as a catalyst in the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. The primary mechanism of fomepizole is to act as a competitive inhibitor of ADH. It is used as an antidote in the treatment of methanol or ethylene glycol poisoning and considered to have few adverse effects (Prod Info fomepizole intravenous injection, 2012; Jacobsen & McMartin, 1996).
    B) Clinical trials have indicated that serum fomepizole concentrations above 15 milligrams/liter have provided complete inhibition of ADH (Shannon, 1998).
    C) In a kinetics study in healthy subjects, fomepizole concentrations in the range of 120 to 260 micromol/liter were able to inhibit ethanol elimination and, thereby, inhibit ADH activity (Jacobsen & McMartin, 1996).

Physicochemical

Physical Characteristics

    A) Fomepizole is a clear to yellow liquid at room temperature; it may be a solid at room temperature (Prod Info Antizol(R), fomepizole , 2000).

Molecular Weight

    A) 82.10

References

General Bibliography

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    2) Benitez JG, Swanson-Biearman B, & Krenzelok EP: Nystagmus secondary to fomepizole administration in a pediatric patient. Clin Toxicol 2000; 38:795-798.
    3) Boyer EW, Mejia M, & Woolf A: Severe ethylene glycol ingestion treated without hemodialysis. Pediatrics 2001; 107:172-174.
    4) Brent J, McMartin K, & Phillips S: Fomepizole for the treatment of ethylene glycol poisoning. New Engl J Med 1999; 340:832-838.
    5) Brophy PD, Tenenbein M, Gardner J, et al: Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kid Dis 2000; 35(5):958-962.
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    11) Jacobsen D, Sebastian CS, & Barron SK: Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. J Emerg Med 1990; 8:455-461.
    12) Jacobsen D, Sebastian CS, & Blomstrand R: 4-methylpyrazole: A controlled study of safety in healthy human subjects after single, ascending doses. Alcoholism Clin Exp Res 1988; 12:516-522.
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    16) Lindros KO, Stowell A, & Pikkarainen P: The disulfiram (antabuse)-alcohol reaction in male alcoholics: Its efficient management by 4-methylpyrazole. Alcoholism: Clin Exp Res 1981; 5:528-530.
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