U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C4H6N2
Molecular Weight 82.1038
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOMEPIZOLE

SMILES

CC1=CNN=C1

InChI

InChIKey=RIKMMFOAQPJVMX-UHFFFAOYSA-N
InChI=1S/C4H6N2/c1-4-2-5-6-3-4/h2-3H,1H3,(H,5,6)

HIDE SMILES / InChI
Fomepizole (4-methylpyrazole) is a competitive ADH inhibitor. Fomepizole has been shown in vitro to block alcohol dehydrogenase enzyme activity in dog, monkey and human liver. Fomepizole is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis. It should be given when a known or suspected toxic ethylene glycol or methanol ingestion has occurred and the patient has metabolic acidosis and elevated osmolar gap. The most frequent adverse events reported as drug-related or unknown relationship were headache (14%), nausea (11%), and dizziness, increased drowsiness, and bad taste/metallic taste. Reciprocal interactions may occur with concomitant use of fomepizole and drugs that increase or inhibit the cytochrome P450 system (e.g. phenytoin, carbamazepine, cimetidine, ketoconazole). Fomepizole has been shown to induce the expression of CYP2E1 and to inhibit its activity. These effects were enhanced in rats that had been exposed to ethanol. Fomepizole may also inhibit other CYP enzymes and therefore may alter the exposure to other drugs that are metabolised by CYP enzymes.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ANTIZOL

Approved Use

Fomepizole injection is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis.

Launch Date

8.8119358E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.5 μg/mL
10 mg/kg 2 times / day steady-state, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOMEPIZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.5 h
10 mg/kg 2 times / day steady-state, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOMEPIZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg/kg single, oral
Highest studied dose
Dose: 100 mg/kg
Route: oral
Route: single
Dose: 100 mg/kg
Sources: Page: p.519
healthy, 25+/-3
n = 4
Health Status: healthy
Age Group: 25+/-3
Sex: M
Population Size: 4
Sources: Page: p.519
DLT: Nausea, Dizziness...
Dose limiting toxicities:
Nausea (grade 1-2, 33%)
Dizziness (grade 1-2, 33%)
Appetite lost (grade 1-2, 33%)
Vertigo (mild, 33%)
Sources: Page: p.519
15 mg/kg 2 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 2 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 2 times / day
Sources:
unhealthy
n = 23
Health Status: unhealthy
Condition: Ethylene glycol poisoning
Sex: M+F
Population Size: 23
Sources:
AEs

AEs

AESignificanceDosePopulation
Appetite lost grade 1-2, 33%
DLT
100 mg/kg single, oral
Highest studied dose
Dose: 100 mg/kg
Route: oral
Route: single
Dose: 100 mg/kg
Sources: Page: p.519
healthy, 25+/-3
n = 4
Health Status: healthy
Age Group: 25+/-3
Sex: M
Population Size: 4
Sources: Page: p.519
Dizziness grade 1-2, 33%
DLT
100 mg/kg single, oral
Highest studied dose
Dose: 100 mg/kg
Route: oral
Route: single
Dose: 100 mg/kg
Sources: Page: p.519
healthy, 25+/-3
n = 4
Health Status: healthy
Age Group: 25+/-3
Sex: M
Population Size: 4
Sources: Page: p.519
Nausea grade 1-2, 33%
DLT
100 mg/kg single, oral
Highest studied dose
Dose: 100 mg/kg
Route: oral
Route: single
Dose: 100 mg/kg
Sources: Page: p.519
healthy, 25+/-3
n = 4
Health Status: healthy
Age Group: 25+/-3
Sex: M
Population Size: 4
Sources: Page: p.519
Vertigo mild, 33%
DLT
100 mg/kg single, oral
Highest studied dose
Dose: 100 mg/kg
Route: oral
Route: single
Dose: 100 mg/kg
Sources: Page: p.519
healthy, 25+/-3
n = 4
Health Status: healthy
Age Group: 25+/-3
Sex: M
Population Size: 4
Sources: Page: p.519
PubMed

PubMed

TitleDatePubMed
Current management of ethylene glycol poisoning.
2001
Caffeine potentiation of allyl alcohol-induced hepatotoxicity. II. In vitro study.
2001
Effect of 4-methylpyrazole on endogenous plasma ethanol and methanol levels in humans.
2001 Apr
Bioactivation and cytotoxicity of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) in isolated rat hepatocytes.
2001 Apr
Bioactivation to free radicals and cytotoxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b).
2001 Feb
Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity.
2001 Feb
[Non-approved antidotes in Japan--Foreign antidotes imported for poisoning countermeasures at the Summit 2000].
2001 Jul
Oxidation of 2,6-dimethylaniline by recombinant human cytochrome P450s and human liver microsomes.
2001 Jun
The metabolism of beta-chloroprene: preliminary in-vitro studies using liver microsomes.
2001 Jun 1
Fomepizole in ethylene glycol intoxication.
2001 Mar
Tissue-specific alterations in the 6-hydroxylation of chlorzoxazone following traumatic brain injury in the rat.
2001 Mar
The role of the liver in the acute effect of alcohol on androgens in women.
2001 May
Inhibition of alcohol dehydrogenase blocks enhanced Gi-protein expression following ethanol treatment in experimental hepatocellular carcinoma in vitro.
2001 Oct
Bioactivation and toxicity in vitro of HCFC-123 and HCFC-141b: role of cytochrome P450.
2001 Oct 15
Mechanism of aerobic transformation of carbon tetrachloride by poplar cells.
2002
Fomepizole therapy for pediatric butoxyethanol intoxication.
2002
Rat ventral prostate microsomal biotransformation of ethanol to acetaldehyde and 1-hydroxyethyl radicals: its potential contribution to prostate tumor promotion.
2002
Formate kinetics in methanol poisoning.
2002
Comparison of the therapeutic efficacy of 4-methylpyrazole and N-acetylcysteine on acetaminophen (paracetamol) hepatotoxicity in rats.
2002
Treatment of a 1,4-butanediol poisoning with fomepizole.
2002
Microsome-mediated oxidation of N-nitrosodiethanolamine (NDELA), a bident carcinogen.
2002 Apr
Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH.
2002 Apr
Differential role of CYP2E1 binders and isoniazid on CYP2E1 protein modification in NADPH-dependent microsomal oxidative reactions: free radical scavenging ability of isoniazid.
2002 Aug
Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat.
2002 Aug
Role of endotoxin in NF-kappaB activation by ethanol in rat hepatocytes.
2002 Aug
Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP).
2002 Aug 9
New developments in the therapy of intoxications.
2002 Feb 28
Increased proteolysis after single-dose exposure with hepatotoxins in HepG2 cells.
2002 Jul 15
Enzyme and receptor antagonists for preventing toxicity from the gamma-hydroxybutyric acid precursor 1,4-butanediol in CD-1 mice.
2002 Jun
Temporal activation of p42/44 mitogen-activated protein kinase and c-Jun N-terminal kinase by acetaldehyde in rat hepatocytes and its loss after chronic ethanol exposure.
2002 Jun
Role of fomepizole in the management of ethylene glycol toxicity.
2002 Mar
Suppression of the contact hypersensitivity response following topical exposure to 2-butoxyethanol in female BALB/c mice.
2002 Mar-Apr
Comparative metabolism of N-tert-butyl-N-[1-(1-oxy-pyridin-4-yl)-ethyl]- and N-tert-butyl-N-(1-phenyl-ethyl)-nitroxide by the cytochrome P450 monooxygenase system.
2002 May
Human choriocarcinoma cell line JEG-3 produces and secretes active retinoids from retinol.
2002 May
Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites.
2002 Nov
The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes.
2002 Nov 10
Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF.
2002 Oct
Treatment of ethylene glycol poisoning.
2002 Sep 1
Rethinking the toxic methanol level.
2003
In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats.
2003 Aug
Ethylene glycol intoxication: case report and pharmacokinetic perspectives.
2003 Dec
Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?
2003 Feb
Cinnamic compound metabolism in human skin and the role metabolism may play in determining relative sensitisation potency.
2003 Feb
Inhalational methanol toxicity in pregnancy treated twice with fomepizole.
2003 Feb
Alcohol potentiates hepatitis C virus replicon expression.
2003 Jul
Acetylation of histone H3 at lysine 9 by ethanol in rat hepatocytes.
2003 Jun 27
In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis.
2003 May-Jun
Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1.
2004 Feb
Patents

Sample Use Guides

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 until ethylene glycol or methanol concentrations are undetectable or have been reduced below 20 mg/dL (ethylene glycol 3.22 mmol/L, methanol 6.24 mmol/L), and the patient is asymptomatic with normal pH. All doses should be administered as a slow intravenous infusion over 30 minutes
Route of Administration: Intravenous
Name Type Language
FOMEPIZOLE
GREEN BOOK   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
FOMEPIZOLE [ORANGE BOOK]
Common Name English
FOMEPIZOLE [JAN]
Common Name English
NSC-760365
Code English
FOMEPIZOLE [GREEN BOOK]
Common Name English
FOMEPIZOLE [MART.]
Common Name English
1H-PYRAZOLE, 4-METHYL-
Systematic Name English
FOMEPIZOLE [VANDF]
Common Name English
FOMEPIZOLE [USAN]
Common Name English
4-Methylpyrazole
Systematic Name English
4-MP
Code English
fomepizole [INN]
Common Name English
FOMEPIZOLE [MI]
Common Name English
Fomepizole [WHO-DD]
Common Name English
ANTIZOL
Brand Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 33388
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
NCI_THESAURUS C471
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
EU-Orphan Drug EU/3/01/040
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
NDF-RT N0000175429
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
FDA ORPHAN DRUG 801320
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
WHO-VATC QV03AB34
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
WHO-ATC V03AB34
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
CFR 21 CFR 522.1004
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
Code System Code Type Description
DAILYMED
83LCM6L2BY
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
WIKIPEDIA
FOMEPIZOLE
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
DRUG BANK
DB01213
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
USAN
BB-65
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
CAS
7554-65-6
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
ChEMBL
CHEMBL1308
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
PUBCHEM
3406
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
MESH
C010238
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
ECHA (EC/EINECS)
231-445-0
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
EVMPD
SUB07775MIG
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
MERCK INDEX
m5523
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY Merck Index
SMS_ID
100000080410
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
FDA UNII
83LCM6L2BY
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
RXCUI
15226
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY RxNorm
CHEBI
5141
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
NCI_THESAURUS
C47538
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
DRUG CENTRAL
1233
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
EPA CompTox
DTXSID3040649
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
INN
6633
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY
NSC
760365
Created by admin on Fri Dec 15 15:31:56 UTC 2023 , Edited by admin on Fri Dec 15 15:31:56 UTC 2023
PRIMARY