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Details

Stereochemistry ACHIRAL
Molecular Formula C4H6N2
Molecular Weight 82.104
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOMEPIZOLE

SMILES

Cc1c[nH]nc1

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
Metabolism of 3-methylindole by porcine liver microsomes: responsible cytochrome P450 enzymes.
2000 Jun
Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole.
2001
Current management of ethylene glycol poisoning.
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
Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity.
2001 Feb
Fomepizole in the treatment of poisoning.
2001 Jan
The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor alpha is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver.
2001 Jan 5
[Ethylene glycol and methanol poisoning. Fomepizole--an alternative antidote].
2001 Jul 25
The metabolism of beta-chloroprene: preliminary in-vitro studies using liver microsomes.
2001 Jun 1
Tissue-specific alterations in the 6-hydroxylation of chlorzoxazone following traumatic brain injury in the rat.
2001 Mar
Functional relevance of human adh polymorphism.
2001 May
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
Childhood methanol ingestion treated with fomepizole and hemodialysis.
2001 Oct
American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.
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
Treatment of a 1,4-butanediol poisoning with fomepizole.
2002
Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH.
2002 Apr
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 Apr 19
PAV-1, a new rat hepatic stellate cell line converts retinol into retinoic acid, a process altered by ethanol.
2002 Aug
Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white men and women: effect of 4-methylpyrazole.
2002 Feb
Accreditation of skin from a methanol-poisoned victim for banking and grafting.
2002 Jun 27
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
The effect of cyanamide and 4-methylpyrazole on the ethanol-induced locomotor activity in mice.
2002 May
Treatment of ethylene glycol poisoning.
2002 Sep 1
Testosterone increases in men after a low dose of alcohol.
2003 Apr
Agitation by sedation.
2003 Jan 25
Pyrazolato-bridged polynuclear palladium and platinum complexes. Synthesis, structure, and reactivity.
2003 Jun 16
Metabolism of chloroform in the human liver and identification of the competent P450s.
2003 Mar
Methanol ingestion: prevention of toxic sequelae after massive ingestion.
2003 May
Interferon gamma enhances proteasome activity in recombinant Hep G2 cells that express cytochrome P4502E1: modulation by ethanol.
2003 Sep 1
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 [WHO-DD]
Common Name 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
ANTIZOL
Brand Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 33388
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
NCI_THESAURUS C471
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
EU-Orphan Drug EU/3/01/040
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
NDF-RT N0000175429
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
FDA ORPHAN DRUG 801320
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
WHO-VATC QV03AB34
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
WHO-ATC V03AB34
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
CFR 21 CFR 522.1004
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
Code System Code Type Description
WIKIPEDIA
FOMEPIZOLE
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
DRUG BANK
DB01213
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
CAS
7554-65-6
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
ChEMBL
CHEMBL1308
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
PUBCHEM
3406
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
MESH
C010238
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
ECHA (EC/EINECS)
231-445-0
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
EVMPD
SUB07775MIG
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
MERCK INDEX
M5523
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY Merck Index
FDA UNII
83LCM6L2BY
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
RXCUI
15226
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C47538
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
DRUG CENTRAL
1233
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
EPA CompTox
7554-65-6
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY
INN
6633
Created by admin on Fri Jun 25 21:30:46 UTC 2021 , Edited by admin on Fri Jun 25 21:30:46 UTC 2021
PRIMARY