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

Details

Stereochemistry ABSOLUTE
Molecular Formula C24H21F2NO3
Molecular Weight 409.4261
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EZETIMIBE

SMILES

c1cc(ccc1[C@]([H])(CC[C@]2([H])[C@@]([H])(c3ccc(cc3)O)N(c4ccc(cc4)F)C2=O)O)F

InChI

InChIKey=OLNTVTPDXPETLC-XPWALMASSA-N
InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/ezetimibe.html

Ezetimibe is an anti-hyperlipidemic medication which is used to lower cholesterol levels. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes. Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZETIA

Approved Use

Ezetimibe, administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia.

Launch Date

1.03541762E12
Primary
ZETIA

Approved Use

Homozygous Familial Hypercholesterolemia (HoFH) The combination of Ezetimibe and atorvastatin or simvastatin is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Launch Date

1.03541762E12
Primary
ZETIA

Approved Use

Ezetimibe is indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia.

Launch Date

1.03541762E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
64.2 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
70.1 ng/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.4 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
726 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
743 ng × h/mL
10 mg 1 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EZETIMIBE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Age Group: 57 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Liver injury...
AEs leading to
discontinuation/dose reduction:
Liver injury
Sources:
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, children
n = 92
Health Status: unhealthy
Condition: Primary hypercholesterolemia
Age Group: children
Population Size: 92
Sources:
Other AEs: Epilepsy congenital, Appendicitis...
Other AEs:
Epilepsy congenital (serious, 1 patient)
Appendicitis (serious, 1 patient)
Upper respiratory tract infection (below serious, 7 patients)
Sources:
50 mg 1 times / day multiple, oral
Highest studied dose
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
unhealthy
n = 15
Health Status: unhealthy
Population Size: 15
Sources:
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy
n = 75
Health Status: unhealthy
Condition: Type 2 Diabetes
Population Size: 75
Sources:
Other AEs: Cataract, Abdominal pain upper...
Other AEs:
Cataract (serious, 1 patient)
Abdominal pain upper (serious, 1 patient)
Type 2 diabetes mellitus (below serious, 7 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Liver injury Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Age Group: 57 years
Sex: M
Population Size: 1
Sources:
Upper respiratory tract infection below serious, 7 patients
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, children
n = 92
Health Status: unhealthy
Condition: Primary hypercholesterolemia
Age Group: children
Population Size: 92
Sources:
Appendicitis serious, 1 patient
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, children
n = 92
Health Status: unhealthy
Condition: Primary hypercholesterolemia
Age Group: children
Population Size: 92
Sources:
Epilepsy congenital serious, 1 patient
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, children
n = 92
Health Status: unhealthy
Condition: Primary hypercholesterolemia
Age Group: children
Population Size: 92
Sources:
Type 2 diabetes mellitus below serious, 7 patients
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy
n = 75
Health Status: unhealthy
Condition: Type 2 Diabetes
Population Size: 75
Sources:
Abdominal pain upper serious, 1 patient
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy
n = 75
Health Status: unhealthy
Condition: Type 2 Diabetes
Population Size: 75
Sources:
Cataract serious, 1 patient
10 mg 1 times / day steady, oral
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy
n = 75
Health Status: unhealthy
Condition: Type 2 Diabetes
Population Size: 75
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
not significant
unlikely (co-administration study)
Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone
Page: 19.0
yes [IC50 0.25 uM]
yes [IC50 2.2 uM]
unlikely
Comment: page 8: R-value extrapolation indicate potential for DDI as unlikely
Page: 11.0
yes [IC50 2.9 uM]
yes [IC50 24 uM]
Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
Molecule of the month. Ezetimibe.
2001 Apr
[Combination therapy of hypercholesterolemia].
2002
The future direction of cholesterol-lowering therapy.
2002 Dec
Gateways to clinical trials.
2002 Nov
Ezetimibe.
2002 Nov
[Improved antilipemic drug is approved. Cholesterol absorption is inhibited].
2002 Nov 14
Combination therapy for combined dyslipidemia.
2002 Nov 20
[Cholesterol resorption inhibition prevents high statin doses. Lipid lowering in double-pack].
2002 Nov 28
[Ezetimib plus statin combination. A strong duo].
2002 Nov 28
[Ezetimib--the first selective cholesterol resorption inhibitors. Strengthening of statins].
2002 Nov 28
Ezetimibe: the first in a novel class of selective cholesterol-absorption inhibitors.
2002 Nov-Dec
New drugs for treating lipid abnormalities.
2002 Nov-Dec
Ezetimibe.
2003 Apr
Ezetimibe potently inhibits cholesterol absorption but does not affect acute hepatic or intestinal cholesterol synthesis in rats.
2003 Apr
Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia.
2003 Apr
Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.
2003 Apr
Combined lipid lowering drug therapy for the effective treatment of hypercholesterolaemia.
2003 Apr
New drug joins cholesterol-fighting arsenal.
2003 Apr
Synthesis of a biotin-tagged photoaffinity probe of 2-azetidinone cholesterol absorption inhibitors.
2003 Apr 17
Beyond statins. New drugs can work with, or in place of, cholesterol-lowering statins.
2003 Feb
Fresh from the pipeline. Ezetimibe.
2003 Feb
Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia.
2003 Feb 15
[The best of clinical pharmacology in 2002].
2003 Jan
A novel therapeutic approach to dyslipidemia.
2003 Jan
Combination therapy for dyslipidemia.
2003 Jan
Treating hypercholesterolemia: looking forward.
2003 Jan
[Lowering cholesterol becomes easier. Combining instead of increasing dosage].
2003 Jan 23
Perspectives in cholesterol-lowering therapy: the role of ezetimibe, a new selective inhibitor of intestinal cholesterol absorption.
2003 Jul 1
Ezetimibe added to ongoing statin therapy reduced LDL cholesterol in primary hypercholesterolemia.
2003 Jul-Aug
Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies.
2003 Jun
Sterol absorption by the small intestine.
2003 Jun
Cholesterol absorption inhibitors: defining new options in lipid management.
2003 Jun
Ezetimibe for management of hypercholesterolemia.
2003 Jun
Combination lipid-lowering therapy in diabetes.
2003 Jun
What future for combination therapies?
2003 Mar
New cholesterol-lowering drug makes its mark.
2003 Mar
New lipid-modifying therapies.
2003 Mar
Three new drugs for hyperlipidemia.
2003 Mar 3
Zetia (ezetimibe).
2003 Mar-Apr
Gateways to clinical trials.
2003 May
Three new drugs for hyperlipidemia.
2003 May
52nd Annual Scientific Session of the American College of Cardiology, Chicago, March 30-April 2, 2003.
2003 May
Statins, super-statins and cholesterol absorption inhibitors.
2003 May
Treating dyslipidemic patients with lipid-modifying and combination therapies.
2003 May
Familial hypercholesterolemia--improving treatment and meeting guidelines.
2003 May
[Controlling LDL cholesterol from 2 sides. "I have never seen such low LDL values"].
2003 May 15
New lipid-lowering combo proves successful.
2003 May 20
Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.
2003 May 20
[Coronary disease prevention: only the inhibition of inflammation is important. Why lower lipids, too?].
2003 May 22
The intestinal absorption of biliary and dietary cholesterol as a drug target for lowering the plasma cholesterol level.
2003 Winter
Patents

Patents

Sample Use Guides

In Vivo Use Guide
10 mg orally once a day
Route of Administration: Oral
10uM/L ezetimibe treatment of Huh7 hepatocytes significantly decreased PA-induced fat accumulation and increased PA-reduced mRNA and protein expression involved in autophagy
Name Type Language
EZETIMIBE
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
EZETIMIBE [USP MONOGRAPH]
Common Name English
EZETIMIBE [JAN]
Common Name English
EZETIMIBE [USAN]
Common Name English
EZETIMIBE [USP-RS]
Common Name English
EZETIMIBE [VANDF]
Common Name English
SCH-58235
Code English
SCH58235
Code English
ROSZET COMPONENT EZETIMIBE
Brand Name English
EZETIMIBE [MI]
Common Name English
EZETIMIBE COMPONENT OF VYTORIN
Brand Name English
NEXLIZET COMPONENT EZETIMIBE
Brand Name English
NSC-758923
Code English
EZETIMIBE [WHO-DD]
Common Name English
EZETIMIBE [ORANGE BOOK]
Common Name English
EZETIMIBE COMPONENT OF NEXLIZET
Brand Name English
EZETIMIBE [MART.]
Common Name English
VYTORIN COMPONENT EZETIMIBE
Brand Name English
ZETIA
Brand Name English
(3R,4S)-1-(P-FLUOROPHENYL)-3-((3S)-3-(P-FLUOROPHENYL)-3-HYDROXYPROPYL)-4-(P-HYDROXYPHENYL)-2-AZETIDINONE
Systematic Name English
EZETROL
Brand Name English
MK0653
Code English
EZETIMIBE COMPONENT OF ROSZET
Brand Name English
EZETIMIBE [HSDB]
Common Name English
2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-(3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL)-4-(4-HYDROXYPHENYL)-, (3R-(3.ALPHA.(S*),4.BETA.))-
Systematic Name English
EZETIMIBE [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000008553
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-ATC C10BA05
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-VATC QC10AX09
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-VATC QC10BA06
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-ATC C10BA06
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-ATC C10BA02
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-ATC C10AX09
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-VATC QC10BA05
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
NCI_THESAURUS C29703
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
WHO-VATC QC10BA02
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
LIVERTOX 396
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
NDF-RT N0000175911
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
Code System Code Type Description
FDA UNII
EOR26LQQ24
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
INN
8010
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
NCI_THESAURUS
C47529
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
JAPANESE REVIEW
ZETIA
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY APPROVE APRIL 2007
USP_CATALOG
1269028
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY USP-RS
PUBCHEM
150311
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
MERCK INDEX
M5228
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY Merck Index
EVMPD
SUB16430MIG
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
CAS
163222-33-1
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL1138
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
HSDB
7737
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
DRUG BANK
DB00973
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
LACTMED
Ezetimibe
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
DRUG CENTRAL
1125
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
EPA CompTox
163222-33-1
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
NDF-RT
N0000008553
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY Decreased Cholesterol Absorption [PE]
RXCUI
341248
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
EZETIMIBE
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
IUPHAR
6816
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY
MESH
C108606
Created by admin on Fri Jun 25 22:04:01 UTC 2021 , Edited by admin on Fri Jun 25 22:04:01 UTC 2021
PRIMARY