FOMEPIZOLE

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 Search

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

Molecular Formula	C4H6N2
Molecular Weight	82.1038
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.rxlist.com/antizol-drug.htm | https://www.tga.gov.au/sites/default/files/auspar-fomepizole-170817-pi.pdf | doi: 10.1016/B978-0-323-08500-7.00095-3

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

Targets

Primary Target	Pharmacology	Condition	Potency
Alcohol dehydrogenase 6 Target ID: CHEMBL2096668 Sources: https://www.tga.gov.au/sites/default/files/auspar-fomepizole-170817-pi.pdf \| doi: 10.1016/B978-0-323-08500-7.00095-3	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ethylene glycol Poisoning 2 Sources: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020696	Primary		Approved 8583	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 1997

C_max

Value	Dose	Analyte	Population
266.36 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
355.94 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
18.5 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15167624	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

AUC

Value	Dose	Co-administered	Analyte	Population
5963 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5922.27 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
21.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, oral dose: 15 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
17.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18344099/	15 mg/kg single, intravenous dose: 15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	FOMEPIZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/15167624	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

Dose	Population	Adverse events
100 mg/kg single, oral Highest studied dose Dose: 100 mg/kg Route: oral Route: single Dose: 100 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/3056073	healthy, 25+/-3 Health Status: healthy Age Group: 25+/-3 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3056073	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: https://pubmed.ncbi.nlm.nih.gov/3056073
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: https://www.aafp.org/afp/1999/0701/p294.html	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.aafp.org/afp/1999/0701/p294.html	Sources: https://www.aafp.org/afp/1999/0701/p294.html

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/3056073	healthy, 25+/-3 Health Status: healthy Age Group: 25+/-3 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3056073
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: https://pubmed.ncbi.nlm.nih.gov/3056073	healthy, 25+/-3 Health Status: healthy Age Group: 25+/-3 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3056073
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: https://pubmed.ncbi.nlm.nih.gov/3056073	healthy, 25+/-3 Health Status: healthy Age Group: 25+/-3 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3056073
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: https://pubmed.ncbi.nlm.nih.gov/3056073	healthy, 25+/-3 Health Status: healthy Age Group: 25+/-3 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3056073

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5141	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5141
ChemicalBook	CB8233079	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8233079
eMolecules	489528	https://www.emolecules.com/cgi-bin/more?vid=489528
MolPort	MolPort-016-633-159	https://www.molport.com/shop/molecule-link/MolPort-016-633-159
ZINC	ZINC000000897288	http://zinc15.docking.org/substances/ZINC000000897288

PubMed

Title	Date	PubMed
Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1.	2004-02	14695664
Ethylene glycol intoxication: case report and pharmacokinetic perspectives.	2003-12	14695045
Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by ethanol.	2003-09-01	12948850
Cytochrome P450-dependent metabolism of l-deprenyl in monkey (Cercopithecus aethiops) and C57BL/6 mouse brain microsomal preparations.	2003-09	12911625
In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats.	2003-08	12960514
Alcohol potentiates hepatitis C virus replicon expression.	2003-07	12829987
Acetylation of histone H3 at lysine 9 by ethanol in rat hepatocytes.	2003-06-27	12804592
Pyrazolato-bridged polynuclear palladium and platinum complexes. Synthesis, structure, and reactivity.	2003-06-16	12793829
Allyl alcohol activation of protein kinase C delta leads to cytotoxicity of rat hepatocytes.	2003-05	12755590
Methanol ingestion: prevention of toxic sequelae after massive ingestion.	2003-05	12745047
In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis.	2003-04-25	12711651
Testosterone increases in men after a low dose of alcohol.	2003-04	12711931
Species variations in cutaneous alcohol dehydrogenases and aldehyde dehydrogenases may impact on toxicological assessments of alcohols and aldehydes.	2003-03-03	12499113
Metabolism of chloroform in the human liver and identification of the competent P450s.	2003-03	12584152
Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?	2003-02	12769509
Cinnamic compound metabolism in human skin and the role metabolism may play in determining relative sensitisation potency.	2003-02	12615359
Inhalational methanol toxicity in pregnancy treated twice with fomepizole.	2003-02	12583693
Agitation by sedation.	2003-01-25	12559866
Antidote review: fomepizole for methanol poisoning.	2003-01-11	12522524
Rethinking the toxic methanol level.	2003	14677789
Fomepizole therapy for reversal of visual impairment after methanol poisoning: a case documented by visual evoked potentials investigation.	2002-12	12470767
The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes.	2002-11-10	12399160
Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites.	2002-11	12386121
[Severe ethylene glycol poisoning treated wtih fomepizole (4-methylpyrazole)].	2002-10-20	12448112
Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF.	2002-10	12394292
Treatment of ethylene glycol poisoning.	2002-09-01	12322772
Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP).	2002-08-09	12036955
Differential role of CYP2E1 binders and isoniazid on CYP2E1 protein modification in NADPH-dependent microsomal oxidative reactions: free radical scavenging ability of isoniazid.	2002-08	12420748
Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat.	2002-08	12296966
Role of endotoxin in NF-kappaB activation by ethanol in rat hepatocytes.	2002-08	12198367
Oxidative bioactivation of crotyl alcohol to the toxic endogenous aldehyde crotonaldehyde: association of protein carbonylation with toxicity in mouse hepatocytes.	2002-08	12184789
Increased proteolysis after single-dose exposure with hepatotoxins in HepG2 cells.	2002-07-15	12106824
Pretreatment of CD-1 mice with 4-methylpyrazole blocks toxicity from the gamma-hydroxybutyrate precursor, 1,4-butanediol.	2002-07-05	12074936
Spectroscopic study on charge transfer molecular complexes of pyrazole derivatives with some pi-electron acceptors.	2002-07	12164488
Accreditation of skin from a methanol-poisoned victim for banking and grafting.	2002-06-27	12131687
Enzyme and receptor antagonists for preventing toxicity from the gamma-hydroxybutyric acid precursor 1,4-butanediol in CD-1 mice.	2002-06	12105121
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.	2002-06	12023518
Fomepizole as an antidote for ethylene glycol poisoning.	2002-06	12022913
Suppression of the contact hypersensitivity response following topical exposure to 2-butoxyethanol in female BALB/c mice.	2002-05-23	12022630
Mediation by nitric oxide of the stimulatory effects of ethanol on blood flow.	2002-05-10	12138012
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.	2002-05	12018998
Central effects of 1,4-butanediol are mediated by GABA(B) receptors via its conversion into gamma-hydroxybutyric acid.	2002-04-26	12063087
Side-chain metabolism of propranolol: involvement of monoamine oxidase and mitochondrial aldehyde dehydrogenase in the metabolism of N-desisopropylpropranolol to naphthoxylactic acid in rat liver.	2002-04-19	12269395
Extracorporeal therapies for acute intoxications.	2002-04	12053840
New developments in the therapy of intoxications.	2002-02-28	12052670
Mechanism of aerobic transformation of carbon tetrachloride by poplar cells.	2002	12688582
Fomepizole therapy for pediatric butoxyethanol intoxication.	2002	12507064
American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.	2002	12216995
Rat ventral prostate microsomal biotransformation of ethanol to acetaldehyde and 1-hydroxyethyl radicals: its potential contribution to prostate tumor promotion.	2002	12210496
Formate kinetics in methanol poisoning.	2002	12126185

Patents

Sample Use Guides

In Vivo Use Guide

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

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:14 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:14 GMT 2025`
Record UNII	83LCM6L2BY
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FOMEPIZOLE

Official Name

English

ANTIZOL

Preferred 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

Classification Tree Code System Code

FDA ORPHAN DRUG

33388